Michael Levin Bioelectricity 101 Crash Course Lesson 21: Notch Mutations and Bioelectricity: Overcoming Genetic Defects Summary
- Notch signaling is a fundamental cell-cell communication pathway essential for many developmental processes, including neurogenesis (the formation of nerve cells).
- Notch is a receptor protein on the cell surface. When it binds to its ligand (another protein) on a neighboring cell, a part of the Notch protein (the Notch Intracellular Domain, or Notch ICD) is cleaved off and goes to the nucleus to regulate gene expression.
- Activated Notch (Notch ICD) often suppresses neural fate – it keeps cells from becoming neurons. This is important for proper patterning, ensuring that not all cells in a region become neurons.
- The Journal of Neuroscience paper showed that overexpressing activated Notch (Notch ICD) in Xenopus embryos disrupts normal brain development and depolarizes the developing neural tube.
- Crucially, hyperpolarizing the cells (by overexpressing ion channels like Kv1.5 or Bir10) could rescue the brain defects caused by activated Notch. This demonstrates a direct interaction between bioelectric state and Notch signaling.
- The Notch pathway can also cause Vmem patterns to change. The pathways can regulate each other.
- The Vmem environment is both required for development to correctly occur, and also sufficient to start creating normal body parts even outside its natural body region
- This rescue suggests that Vmem can, in some cases, override genetic signals or disruptions in biochemical pathways. It highlights the power of bioelectric signals as a control point in development.
- This reinforces the idea of bioelectricity as a “software” layer that can, to some extent, reprogram cell behavior even with faulty “hardware” (genetic mutations or disrupted pathways).
- The rescue does involve both Calcium and GJ interelations
- This has important implications for understanding and potentially treating birth defects caused by genetic mutations or disruptions in signaling pathways.
Michael Levin Bioelectricity 101 Crash Course Lesson 21: Notch Mutations and Bioelectricity: Overcoming Genetic Defects
We’ve been on an incredible journey exploring the world of bioelectricity, learning how the electrical language of cells shapes life far beyond the rapid-fire signals of the nervous system. We’ve seen how steady-state voltage gradients act as an “electrical blueprint” guiding development and regeneration. We’ve delved into the roles of specific ion channels, like HCN2, in rescuing developmental defects. Now, we’re going to take another crucial step, exploring the fascinating interaction between bioelectricity and a fundamental cell signaling pathway called Notch, and demonstrating the remarkable potential to overcome genetic defects by manipulating bioelectric signals.
Let’s start by understanding Notch signaling. Imagine two cells sitting next to each other. One cell has a protein on its surface called the Notch receptor. Think of it like a lock. The other cell has a protein on its surface that acts like a key – this is called the Notch ligand (examples include Delta and Jagged). When the ligand on one cell binds to the Notch receptor on the neighboring cell, it’s like the key fitting into the lock and turning.
This “turning of the key” triggers a series of events inside the cell with the Notch receptor. A part of the Notch receptor inside the cell, called the Notch Intracellular Domain (Notch ICD), is cleaved off. This Notch ICD is like a messenger. It travels to the cell’s nucleus (where the DNA is) and acts as a transcription factor. That means it binds to DNA and influences which genes are turned “on” or “off.”
So, in short: Notch ligand on one cell binds to Notch receptor on a neighboring cell → Notch ICD is released → Notch ICD goes to the nucleus and regulates gene expression. This is a fundamental way that cells communicate with their direct neighbors and coordinate their behavior during development.
Now, what does Notch signaling do? It plays many roles, but one of its key functions is in controlling cell fate – deciding what type of cell a cell will become. In the context of neurogenesis (the formation of nerve cells), Notch signaling often acts as a suppressor of neural fate. It’s like a “brake” that prevents cells from becoming neurons.
Why would you want to prevent cells from becoming neurons? It sounds counterintuitive, but it’s essential for proper patterning. Imagine a group of cells that are all capable of becoming neurons. If all of them became neurons, you’d have a disorganized mass of nerve cells. You need a way to create a pattern, where some cells become neurons and others become different cell types (like supporting glial cells).
Notch signaling helps achieve this through a process called lateral inhibition. When a cell starts to become a neuron, it expresses more of the Notch ligand on its surface. This activates Notch signaling in its neighbors, suppressing their neural fate. It’s like the cell saying, “I’m becoming a neuron, so you don’t!” This creates a pattern where some cells become neurons and others don’t, ensuring the proper balance and organization of cell types.
Now, let’s connect this back to bioelectricity. The Journal of Neuroscience paper we summarized investigated the role of endogenous bioelectric gradients in brain development. They found, as we discussed in previous lessons, that the cells lining the developing neural tube are naturally hyperpolarized (more negative Vmem) compared to surrounding tissues. Disrupting this pattern, by either hyperpolarizing or depolarizing the cells, caused brain malformations.
Here’s where it gets really interesting. The researchers took embryos and overexpressed a constitutively active form of Notch (Notch ICD). This means that the Notch signaling pathway was constantly “on” in those cells, even without the need for the ligand to bind. This is like having the “brake” on neural development constantly engaged.
What happened? As you might expect, overexpressing Notch ICD caused severe brain defects. But, crucially, they also found that Notch ICD depolarized the developing neural tube. It disrupted the normal hyperpolarized Vmem pattern.
This is a key connection! It shows that Notch signaling, a fundamental biochemical pathway, can directly influence the bioelectric state of cells. And, as we’ve learned, the bioelectric state is a powerful regulator of development.
But here’s the most remarkable part. The researchers then asked: could they rescue the brain defects caused by Notch ICD by restoring the normal hyperpolarization? They used the same strategy we discussed in the previous lesson: overexpressing hyperpolarizing ion channels (Kv1.5 and Bir10) in the same cells where Notch ICD was overexpressed.
And it worked! Restoring the hyperpolarization, even in the presence of activated Notch, significantly reduced the brain malformations. This is a stunning result. It shows that, in this context, the bioelectric signal can override the biochemical signal. Even though the Notch pathway was constantly telling the cells not to become neurons, the hyperpolarized Vmem was a stronger signal, pushing them back towards a neural fate. This demonstrated experimentally that voltage state of a cell (and also the landscape) can trump strong biochemical influence.
This can be represented as a feedback model;
- Bioelectricity of the cells can help influence and differentiate certain important developmental transcription factors.
- However, as the body develops and transcription occurs, some of these will change the bioelectricity environment. In this example, increasing amounts of activated Notch depolarizes the neural cells!
- Coexpression with activated Notch and further depolarization made the outcomes even more severe and defective!
- Conversely, coexpression of just an increased hyperpolarizing factors caused significantly less issues for growth than controls – in some situations the results were indistinguishable from control!
- It can be thought to have an effect across distance
- Certain factors that block direct neighbor-to-neighbor connection through GJs and calcium flux can help lessen the problem.
This has profound implications. It suggests that in some cases, we might be able to correct developmental defects caused by genetic mutations or disruptions in signaling pathways by manipulating the bioelectric state of cells. It highlights the potential of “bioelectric medicine” as a new approach to treating birth defects.
Think back to the analogy of the “hardware” and “software” of life. The genome is the hardware – the physical components. Bioelectricity is like the software – the instructions and information processing that tell the hardware what to do. This research suggests that even if there’s a problem with the hardware (a genetic mutation or a disrupted signaling pathway), we might be able to “reprogram” the cells by changing the software (the bioelectric state).
This isn’t to say that bioelectricity is a “magic bullet” that can fix all genetic defects. But it does demonstrate that bioelectric signals are a powerful, and often overlooked, factor in development and that they can, in some cases, override or compensate for genetic or biochemical disruptions. It opens up a whole new way of thinking about development, disease, and regenerative medicine.
Michael Levin Bioelectricity 101 Crash Course Lesson 21: Notch Mutations and Bioelectricity: Overcoming Genetic Defects Quiz
1. Notch signaling is best described as:
A) A way for cells to communicate with distant tissues.
B) A fundamental cell-cell communication pathway.
C) A type of ion channel.
D) A method for measuring membrane potential.
2. The Notch Intracellular Domain (Notch ICD) acts as a:
A) Neurotransmitter
B) Transcription factor
C) Ion channel
D) Growth factor
3. In the context of neurogenesis, activated Notch often:
A) Promotes neural fate.
B) Suppresses neural fate.
C) Has no effect on neural fate.
D) Causes cells to migrate.
4. Overexpressing activated Notch ICD in Xenopus embryos caused:
A) Increased brain size.
B) Brain malformations.
C) No change in brain development.
D) Enhanced learning ability.
5. Overexpressing Notch in Xenopus will result in
A) Depolarization
B) Hyperpolarizatoin
C) Increased GJ channels.
D) No bioelectrical effect.
6. The brain defects caused by activated Notch could be rescued by:
A) Depolarizing the cells.
B) Hyperpolarizing the cells.
C) Blocking Notch signaling.
D) Increasing serotonin levels.
7. Which ion channels were used to hyperpolarize cells in the rescue experiments?
A) HCN2 and Nav1.5
B) Kv1.5 and Bir10
C) GlyR and nAChR
D) DN-SERT and H7
8. The rescue of brain defects by hyperpolarization demonstrates:
A) That bioelectric signals are unimportant in development.
B) That bioelectric signals can sometimes override genetic or biochemical disruptions.
C) That Notch signaling is the only factor controlling brain development.
D) That Xenopus embryos are resistant to teratogens.
9. What describes best a summary of both necessity, sufficiency and rescue bioelectricity on developing organisms in this experiment and others seen earlier?
A) It demonstrates how bioelectricity, by itself, plays little effect in patterning organisms
B) Bioelectric conditions were found necessary, sufficient to even grow parts in wrong positions, and also showed it can partially rescue and significantly ameloriate damaged tissues.
C) The relationship can be best summed as noise, affecting in an uncontrolled and stochastic fashion.
D) All of the Above.
10. The experiments discussed support the idea of bioelectricity as a:
A) “Hardware” layer that determines the physical structure of cells.
B) “Software” layer that can influence cell behavior even with faulty “hardware.”
C) Minor factor that has little impact on development.
D) Type of chemical signaling pathway.
11. Blocking what was shown to also increase ability to develop normal brains in activated-Notch cells??
A) GJs and Calcium Channels
B) Sodium-potassium pumps
C) nACHRs
D) None of the Above
12. What is lateral inhibition, and what part of this whole picture does that describe?
A) When developing cells release stress-causing compounds to the environment, to stunt neighbors
B) How one cell communicates and changes its neighbor’s state – typically it inhibits cells touching it, from developing in a similar direction
C) How Vmem acts at a distance, by pushing on distant neighbors
D) None of The Above.
13. A major research component used in the experiments was the Usage of..
A) Crispr on tadpoles
B) Electrophysiological probing of cell slices.
C) Using in situ to determine which and to where developmental signals occur
D) All of the Above
14. Can expressing active-Notch, and adding extra depolarization have any kind of outcome??
A) It may kill tadpoles
B) The study didn’t investigate.
C) It made development even worse.
D) Yes, with the depolarization helping growth.
15. True or False: Expressing factors like Kv1.5 can rescue issues caused by other biochemical disruptions
A) True
B) False.
16. Vmem is both an _______ of changes, and can also function as an upstream ______ , regulating behavior on cell differentiation:
A) upstream, downstream
B) effect, signal
C) input, variable
D) output, downstream
17. True or False, that based on experimental observation and evidence, manipulating voltages in vivo is thought to, and have evidence that supports that can help encourage and cause proper organization
A) True
B) False
18. Improper neural patterning, if early enough in formation, can result in: A) Spina bifida B) small brains C) anencephaly D) All of the Above.
19. What did immunohistochemistry and the Fucci analysis reveal?
A) That cells died.
B) That it showed, by applying markers of cellular division activity, about the Vmem state’s effects on proliferation state of surrounding cells
C) That nothing could occur outside neural area
D) None of The Above.
20. The research suggests that Vmem state…
A) May have influence of brain sizing
B) Shows, that there is likely a complex multi-layered connection and regulation network for brain sizes and its proper growth.
C) Show how long-distance suppression of growth/proliferation also helps size restriction for correct morphogenesis.
D) All of the Above.
Michael Levin Bioelectricity 101 Crash Course Lesson 21: Notch Mutations and Bioelectricity: Overcoming Genetic Defects Answer Sheet
1. B
2. B
3. B
4. B
5. A
6. B
7. B
8. B
9. B
10. B
11. A
12. B
13. C
14. C
15. A
16. B
17. A
18. D
19. B
20. D
迈克尔·莱文 生物电 101 速成课程 第21课：Notch 突变和生物电：克服遗传缺陷 摘要
- Notch 信号传导是一种基本的细胞间通讯途径，对许多发育过程至关重要，包括神经发生（神经细胞的形成）。
- Notch 是细胞表面的受体蛋白。当它与相邻细胞上的配体（另一种蛋白质）结合时，Notch 蛋白的一部分（Notch 细胞内域，或 Notch ICD）会被切割下来，并进入细胞核以调节基因表达。
- 激活的 Notch（Notch ICD）通常会抑制神经命运——它阻止细胞变成神经元。这对于正确的模式形成非常重要，确保并非一个区域中的所有细胞都变成神经元。
- 《神经科学杂志》的论文表明，在非洲爪蟾胚胎中过表达激活的 Notch (Notch ICD) 会破坏正常的大脑发育，并使发育中的神经管去极化。
- 至关重要的是，超极化细胞（通过过表达离子通道，如 Kv1.5 或 Bir10）可以拯救由激活的 Notch 引起的大脑缺陷。这表明生物电状态和 Notch 信号传导之间存在直接相互作用。
- Notch 通路也会导致 Vmem 模式改变。这些通路可以相互调节。
- Vmem 环境既是发育正确发生的必要条件，也足以开始在自然身体区域之外创建正常的身体部位
- 这种拯救表明 Vmem 在某些情况下可以覆盖遗传信号或生化途径中的破坏。它突出了生物电信号作为发育控制点的力量。
- 这强化了生物电作为“软件”层的观点，它可以在一定程度上重新编程细胞行为，即使存在有缺陷的“硬件”（基因突变或破坏的通路）。
- 这种拯救确实涉及钙离子和间隙连接的相互作用。
- 这对于理解和潜在地治疗由基因突变或信号通路破坏引起的出生缺陷具有重要意义。
迈克尔·莱文 生物电 101 速成课程 第21课：Notch 突变和生物电：克服遗传缺陷
我们一直在探索生物电的神奇世界，了解细胞的电语言如何塑造生命，远远超出了神经系统快速发射信号的范围。我们已经看到稳态电压梯度如何充当“电蓝图”，指导发育和再生。我们已经深入研究了特定离子通道（如 HCN2）在拯救发育缺陷中的作用。现在，我们将采取另一个关键步骤，探索生物电和称为 Notch 的基本细胞信号通路之间迷人的相互作用，并展示通过操纵生物电信号克服遗传缺陷的非凡潜力。
让我们从了解 Notch 信号传导开始。想象一下两个相邻的细胞。一个细胞的表面有一种叫做 Notch 受体的蛋白质。可以把它想象成一把锁。另一个细胞的表面有一种充当钥匙的蛋白质——这被称为 Notch 配体（例子包括 Delta 和 Jagged）。当一个细胞上的配体与相邻细胞上的 Notch 受体结合时，就像钥匙插入锁中并转动一样。
这种“钥匙的转动”会触发 Notch 受体所在细胞内的一系列事件。Notch 受体内部的一部分，称为 Notch 细胞内域 (Notch ICD)，会被切割下来。这个 Notch ICD 就像一个信使。它会进入细胞核（DNA 所在的位置）并充当转录因子。这意味着它与 DNA 结合并影响哪些基因被“打开”或“关闭”。
简而言之：一个细胞上的 Notch 配体与相邻细胞上的 Notch 受体结合 → Notch ICD 被释放 → Notch ICD 进入细胞核并调节基因表达。这是细胞与其直接邻居交流并在发育过程中协调其行为的一种基本方式。
那么，Notch 信号传导做什么呢？它扮演着许多角色，但它的一个关键功能是控制细胞命运——决定细胞将变成什么类型的细胞。在神经发生（神经细胞的形成）的背景下，Notch 信号传导通常充当神经命运的抑制剂。它就像一个“刹车”，阻止细胞变成神经元。
为什么要阻止细胞变成神经元？这听起来有悖常理，但对于正确的模式形成至关重要。想象一组都能够变成神经元的细胞。如果所有细胞都变成了神经元，你就会得到一团杂乱无章的神经细胞。你需要一种方法来创建一个模式，其中一些细胞变成神经元，而另一些细胞变成不同的细胞类型（如支持性神经胶质细胞）。
Notch 信号传导通过一种称为侧向抑制的过程来帮助实现这一点。当一个细胞开始变成神经元时，它会在其表面表达更多的 Notch 配体。这会激活其邻居中的 Notch 信号传导，抑制它们的神经命运。这就像细胞在说，“我要变成神经元，所以你不要！”这创造了一种模式，其中一些细胞变成神经元，而另一些细胞不变成神经元，从而确保细胞类型的适当平衡和组织。
现在，让我们将其与生物电联系起来。我们总结的《神经科学杂志》论文研究了内源性生物电梯度在大脑发育中的作用。他们发现，正如我们在之前的课程中讨论的那样，发育中神经管内壁的细胞相对于周围组织自然超极化（Vmem 更负）。通过超极化或去极化细胞来破坏这种模式会导致大脑畸形。
这就是它真正有趣的地方。研究人员提取了胚胎并过表达了一种组成型激活形式的 Notch (Notch ICD)。这意味着 Notch 信号通路在这些细胞中持续“开启”，即使不需要配体结合。这就像让神经发育的“刹车”一直踩着。
发生了什么？正如你可能预料到的，过表达 Notch ICD 会导致严重的大脑缺陷。但是，至关重要的是，他们还发现 Notch ICD 会使发育中的神经管去极化。它破坏了正常的超极化 Vmem 模式。
这是一个关键的联系！它表明 Notch 信号传导（一种基本的生化途径）可以直接影响细胞的生物电状态。而且，正如我们所了解的，生物电状态是发育的强大调节剂。
但最了不起的部分是。研究人员随后问道：他们能否通过恢复正常的超极化来拯救由 Notch ICD 引起的大脑缺陷？他们使用了我们在上一课中讨论的相同策略：在过表达 Notch ICD 的相同细胞中过表达超极化离子通道（Kv1.5 和 Bir10）。
它起作用了！即使在激活的 Notch 存在的情况下，恢复超极化也能显著减少脑畸形。这是一个惊人的结果。它表明，在这种情况下，生物电信号可以覆盖生化信号。即使 Notch 通路不断地告诉细胞不要变成神经元，超极化的 Vmem 也是一个更强的信号，将它们推回神经命运。这通过实验证明了细胞（以及景观）的电压状态可以胜过强大的生化影响。
这可以表示为一个反馈模型;
- 细胞的生物电可以帮助影响和分化某些重要的发育转录因子。
- 但是，随着身体的发育和转录的发生，其中一些会改变生物电环境。在这个例子中，增加数量的激活 Notch 会使神经细胞去极化！
- 与激活的 Notch 共表达并进一步去极化会使结果更严重和更有缺陷！
- 相反，仅共表达增加的超极化因子会导致比对照组少得多的生长问题 – 在某些情况下，结果与对照组没有区别！
- 可以认为它具有跨距离的影响
- 阻断通过间隙连接和钙离子流进行直接邻里通信的某些因素可以帮助减轻问题。
这具有深远的意义。这表明，在某些情况下，我们也许可以通过操纵细胞的生物电状态来纠正由基因突变或信号通路破坏引起的发育缺陷。它突出了“生物电医学”作为治疗出生缺陷的新方法的潜力。
回想一下生命“硬件”和“软件”的类比。基因组是硬件——物理组件。生物电就像软件——告诉硬件做什么的指令和信息处理。这项研究表明，即使硬件出现问题（基因突变或信号通路中断），我们也许也可以通过改变软件（生物电状态）来“重新编程”细胞。
这并不是说生物电是可以修复所有遗传缺陷的“灵丹妙药”。但它确实表明生物电信号是发育中一个强大的、经常被忽视的因素，并且在某些情况下，它们可以覆盖或补偿遗传或生化破坏。它开启了一种全新的思考发育、疾病和再生医学的方式。
迈克尔·莱文 生物电 101 速成课程 第21课：Notch 突变和生物电：克服遗传缺陷 小测验
1. Notch 信号传导最好描述为：
A) 细胞与远距离组织通信的一种方式。
B) 一种基本的细胞间通信途径。
C) 一种离子通道。
D) 一种测量膜电位的方法。
2. Notch 细胞内域 (Notch ICD) 充当：
A) 神经递质
B) 转录因子
C) 离子通道
D) 生长因子
3. 在神经发生的背景下，激活的 Notch 通常：
A) 促进神经命运。
B) 抑制神经命运。
C) 对神经命运没有影响。
D) 导致细胞迁移。
4. 在非洲爪蟾胚胎中过表达激活的 Notch ICD 会导致：
A) 脑容量增加。
B) 脑畸形。
C) 大脑发育没有变化。
D) 学习能力增强。
5. 在非洲爪蟾中过表达 Notch 会导致
A) 去极化
B) 超极化
C) 间隙连接通道增加。
D) 没有生物电效应。
6. 由激活的 Notch 引起的大脑缺陷可以通过以下方式拯救：
A) 使细胞去极化。
B) 使细胞超极化。
C) 阻断 Notch 信号传导。
D) 增加血清素水平。
7. 在拯救实验中使用了哪些离子通道来使细胞超极化？
A) HCN2 和 Nav1.5
B) Kv1.5 和 Bir10
C) GlyR 和 nAChR
D) DN-SERT 和 H7
8. 通过超极化拯救大脑缺陷表明：
A) 生物电信号在发育中不重要。
B) 生物电信号有时可以覆盖遗传或生化破坏。
C) Notch 信号传导是控制大脑发育的唯一因素。
D) 非洲爪蟾胚胎对致畸剂有抵抗力。
9. 什么最好地描述了本实验和之前看到的实验中生物电对发育中生物体的必要性、充分性和拯救的总结？
A) 它展示了生物电本身如何对模式生物体影响很小
B) 发现生物电条件是必要的，足以甚至在错误的位置生长部分，并且还表明它可以部分拯救并显著改善受损组织。
C) 这种关系最好概括为噪声，以不受控制和随机的方式影响。
D) 以上都是。
10. 所讨论的实验支持将生物电视为：
A) 决定细胞物理结构的“硬件”层。
B) 即使存在有缺陷的“硬件”，也可以影响细胞行为的“软件”层。
C) 对发育影响很小的次要因素。
D) 一种化学信号通路。
11. 阻断什么也被证明可以增加激活 Notch 细胞中正常大脑发育的能力？？
A) 间隙连接和钙离子通道
B) 钠钾泵
C) nACHRs
D) 以上都不是
12. 什么是侧向抑制，这描述了整个图景的哪一部分？
A) 当发育中的细胞向环境释放导致压力的化合物时，会抑制邻居
B) 一个细胞如何交流并改变其邻居的状态 – 通常它会抑制与其接触的细胞，使其无法朝着相似的方向发展
C) Vmem 如何通过推动远处的邻居而在远处起作用
D) 以上都不是。
13. 实验中使用的主要研究组成部分是使用..
A) 对蝌蚪进行 CRISPR
B) 对细胞切片进行电生理探测。
C) 使用原位确定哪些以及发育信号发生的位置
D) 以上都是
14. 表达活性 Notch 并添加额外的去极化会产生任何结果吗？？
A) 它可能会杀死蝌蚪
B) 该研究没有调查。
C) 它使发展变得更糟。
D) 是的，去极化有助于生长。
15. 对或错：表达像 Kv1.5 这样的因子可以拯救由其他生化破坏引起的问题
A) 对
B) 错。
16. Vmem 既是变化的 _______，也可以充当上游 _______，调节细胞分化行为：
A) 上游，下游
B) 效应，信号
C) 输入，变量
D) 输出，下游
17. 对或错，根据实验观察和证据，操纵体内电压被认为，并且有证据支持可以帮助鼓励和导致正确的组织
A) 对
B) 错
18. 如果在形成早期，神经模式形成不当，可能会导致：
A) 脊柱裂 B) 小脑 C) 无脑畸形 D) 以上都是.
19. 免疫组织化学和 Fucci 分析揭示了什么？
A) 细胞死亡。
B) 它通过应用细胞分裂活动标记物，显示了 Vmem 状态对周围细胞增殖状态的影响
C) 神经区域外不可能发生任何事情
D) 以上都不是。
20. 研究表明 Vmem 状态…
A) 可能对大脑大小有影响
B) 表明，对于大脑大小及其正常生长，可能存在复杂的多层连接和调节网络。
C) 展示了长距离抑制生长/增殖也有助于尺寸限制以实现正确的形态发生。
D) 以上都是。
迈克尔·莱文 生物电 101 速成课程 第21课：Notch 突变和生物电：克服遗传缺陷 答案表
1. B
2. B
3. B
4. B
5. A
6. B
7. B
8. B
9. B
10. B
11. A
12. B
13. C
14. C
15. A
16. B
17. A
18. D
19. B
20. D