胚胎发育

2024-07-16 08:11| 来源: 网络整理| 查看: 265

前言：

胚胎发育，主要研究人和小鼠，即从受精卵到胚胎，到产后，最后到成熟体。三种主要的时期：胚胎时期E，产后发育期P，成熟到衰老期Adult。

大脑神经系统很复杂，我们擅长的只有ENS肠道神经系统，ENS的祖先就是neural crest cell。所以我们研究的其实就是neural crest的前世今生，neural tube的形成，分离，迁移，分化。

所以研究的时间起点就是E7左右，即neural crest正式形成的时间点。研究哪个时期还是取决于你的疾病，表型形成的关键时期。

人和鼠胚胎发育的三个关键时期：

(0-8 wks) The embryonic stage begins with fertilization and lasts for eight weeks (10-43wks) From the 10th week of pregnancy (if you’re counting from the start of the last period) until birth is the fetal stage (43wks-) A rapid and complex transition happens at birth, from dependent fetus to independent newborn

两个关键概念的区别：

Fertilization describes the process by which a single sperm gradually penetrates the layers of an egg to form a new cell ("zygote"). Implantation of the preembryo in the uterine lining begins about five days after fertilization. Implantation can be completed as early as eight days or as late as 18 days after fertilization, but usually takes about 14 days. Between one-third and one-half of all fertilized eggs never fully implant. A pregnancy is considered to be established only after implantation is complete.

几类神经系统：

central nervous system (CNS) peripheral nervous system (PNS) enteric nervous system (ENS) 属于PNS的一个分支，那篇organgenesis的paper就是这么归类的。 autonomic nervous system (ANS)

The enteric nervous system (ENS) is a large division of the peripheral nervous system (PNS) that can control gastrointestinal behaviour independently of central nervous system (CNS) input.

ENS与autonomic和sensory的关系？都有

The enteric nervous system (ENS) or intrinsic nervous system is one of the main divisions of the autonomic nervous system (ANS) and consists of a mesh-like system of neurons that governs the function of the gastrointestinal tract.[1] It is capable of acting independently of the sympathetic and parasympathetic nervous systems, although it may be influenced by them. The ENS is also called the second brain.[2][3] It is derived from neural crest cells.[4][5]Although GI functions are controlled by the autonomic nervous system and occur, by and large, independently of conscious perception, it is clear that the sympathetic and parasympathetic regulation and modulation of the GI tract are modulated by higher CNS centers that influence homeostatic control as well as cognitive and behavioral functions.

做这部分的科研必须要把这个问题搞得一清二楚，当前到底研究到什么地步了？

从胚胎发育的起源到成熟个体大脑中各种subtype的细胞类型的作用。

entoderm 内 mesoderm 中 ectoderm 外

分清两个发育过程：

生命发育，就是个体的其他器官的发育智能发育，特指神经系统地发育

The single-cell transcriptional landscape of mammalian organogenesis - introduction

The implantation of the blastocyst on embryonic day (E) 4.0 is followed by gastrulation and the formation of germ layers on E6.5–E7.51,2 . At the early-somite stages, the embryo transits from gastrulation to early organogenesis, forming the neural plate and heart tube (E8.0–E8.5). In the ensuing days (E9.5–E13.5), the embryo expands from hundreds-of-thousands to over ten million cells, and concurrently develops nearly all major organ systems. Unsurprisingly, these four days have been intensively studied. Indeed, most genes that underlie major developmental defects can be studied in this window3,4.

首先，看一下成熟的人和老鼠体内的神经系统是什么样的；

Nervous System - 粗略大概

Nervous System - 3D

其次，每部分的神经系统里面各有哪些subtype的神经细胞；

Nervous system physiology Khan Academy - 神经系统生理学

Neuronal subtype specification in the cerebral cortex

Neuronal subtypes and diversity revealed by single-nucleus RNA sequencing of the human brain

Neuronal subtype specification in establishing mammalian neocortical circuits

最后，这些神经细胞是如何一步一步从受精卵发育而来的；

这就是我要做的工作

Development of the Nervous System - 在线阅读，看书是学习最快的方法

另附一门课程：Medical Neuroscience

neuron structure神经元结构

soma - cell body 细胞躯体

neurite - 神经突起

dentrite and axon - 树突和轴突

hillock - 突起与soma连接的部分

myelin - 髓鞘

ranvier - gap of myelin

synapse - 突触，不是递质

neural stem cell -> neuroblast -> unipolar -> bipolar -> multiplor -> pseudo-unipolar

neuron function神经元功能

gun and target 枪靶

resting membrane potential 静止膜电位，外正内负

graded potential 级量点位

neurotransmitter 神经递质

整体分类

afferent 传入 and sensory 感觉 efferent：motor and autonomic interneuron neuron types常见神经元类型

Astrocytes - star cells，glial cells，derive from neural stem cells，end feet特征，form the scaffold of CNS，CNS中的保姆细胞；

Microglia - small glue，very small，mesoderm

Ependymal cells - 室管膜细胞，也是glial cells，epithelium表层

Oligodendrocytes - 少突细胞，也是glial cells，连接

Schwann cells - 许旺细胞，PNS的glial cells，derive from neural crest cells，单独包裹

Neuron resting potential电位

神经细胞膜，外正内负。将膜外电压设为0，则膜内电压大约为-60mV。

由一些核心的离子iron来维持电压，特定的离子通道非常重要。

胞外环境就像大海，离子的进出只会改变胞内的浓度，胞外的大海的改变可以忽略不计。

Neuron graded potential

级量电位幅值随阈上刺激强度的增大而变高，而反应频率不发生变化的电位。与动作电位不同，不是可传递神经信息的表达形式，只能引起感受器或突触后膜的局部兴奋性变化。这种变化可以发生时间和空间总和，最终导致突触后神经元的发放或与此相联系的感觉神经元的兴奋。

Neuron action potential

动作电位，形式固定，有髓鞘绝缘，可以传递得很快很远。

总结：释放的神经递质会通过离子蛋白来改变神经元膜上的电位，电位达到一个阈值就会产生动作电位，动作电位可以在轴突里高速传递，直到抵达突触，释放神经递质，影响靶细胞。

Effects of axon diameter and myelination

影响传递速度的两个因素

Action potential patterns

和计算机科学高度相关，多个输入信号如何整合成输出信号。

Synapse structure突触结构

有两个类型：

chemical electrical

cleft

Types of neurotransmitters amino acids: glutamate, gamma-aminobutryic (GABA), glycine [两种功能：depolarization, excite; inhibitory, hyperpolarization] peptides monoamines

Types of neurotransmitter receptors

Neurotransmitter removal

Neuroplasticity

Membrane Receptors

Ligand Gated Ion Channels

G Protein Coupled Receptors

Enzyme Linked Receptors