Welcome to this tutorial on early brain development. This topic today will relate to several of our core concepts in the field of neuroscience. in this session, we're going to talk about how neurons communicate, but in a different context than what we did in Neural Two. So, yes, indeed, neurons communicate using both electrical and chemical signals, but today, we're going to focus on the earliest events that led to the development of the nervous system, and we will explore, in some detail, a means of chemical communication that doesn't involve synapses, but it's cell to cell communication via chemicals nevertheless. And, it is a mode of signaling that results in the acquisition of cellular identity, cellular fate, and the regional specification of structure in the developing brain. I think you'll find that a fascinating example of how specific molecules can be used to build a brain. Well, we will also be talking about the expression of specific genes in the the developing brain. So, in a sense, we can apply actually, core concept number three, that genetically determined circuits are the foundation of the nervous system. we will not be talking about the formation of circuits, in this tutorial, we'll save that for a later one. But, we will definitely be exploring examples, where the specific expression of genes is essential for building the foundations of the central nervous system. And then lastly, I think the core concept that I'd like to allude to, just briefly as we go through this tutorial, is that life experiences can change the nervous system, and the kinds of life experiences that I have in mind here are not the sensory motor experiences that we've been talking about in the last couple of units of this course, but, rather the environment that the developing brain might find itself in depending upon factors such as diet the presence of environmental toxins. We can think of these as being very early life experiences that can shape the formation of the brain, unfortunately, often for the worse. Well, okay, with that as a bit of context, let's look at our learning objectives for this tutorial. first I want you to be able to characterize the events that occur during some really important stages of early embryonic development called gastrulation and neurulation. I want you to be able to state the significance of neuroinduction. This is a really important process that I'd like for you to be able to understand and, and be able to discuss with a friend or a family member as a result of this tutorial, and neural induction is one of the key mechanisms that leads to the initial development of the central nervous system. Thirdly, I'd like to be able to have you discuss the factors that guide the migration of neuroblasts, which are the primordial cells that will give rise to the neurons and glia of the brain, and they have to migrate to get to their final destinations. So, I want you to be able to have some capacity to discuss how, how that happens, how they migrate through the developing nervous system. I want you to be able to characterize the cellular mechanisms that influence the differentiation of neurons and glia. Obviously, they are distinct type of cells in the nervous system that serve distinct functions. And in some point in development, cells need to make a decision about what kind of cell they will become, a neuron or a glia, and we're beginning to gain some insight as to how that happens. And then, lastly, in this tutorial, I want you to be able to describe the role of programmed cell death, we call that apoptosis, and the development of the central nervous system. Obviously, we have an aggressive and ambitious agenda for this tutorial, so let's go ahead and get started. And, I'd like to set the state by talking in very broad terms about what I consider to be the three major forces that shape the developing brain and I might even argue that these forces are critical for shaping the evolution of the mammalian brain, but that's a different topic for a different day. In the context of development, I want you to consider how these forces interact, and we will return to this theme as we progress on through our unit on the changing brain. So, let me introduce these ideas and give you a sense of what I have in mind here. So, when we think about the factors that shape the developing brain, I think a lot of us might come quite quickly to the notion of, well, okay, there's nature and there's nurture. But, what do we really mean by these terms? Well, by nature what I mean are, lineage derived signals that reflect the expression of specific genes. so, these are genetic instructions, or what I like to call genetic specification. Okay, so nature reflects the genome that a cell has inherited from its parent cell and there are specific patterns of gene expression that are responsible for much of the early formation of the nervous system. We'll spend a lot of time in this tutorial emphasizing this particular force in brain development. Well, as the developing nervous system acquires a functional capacity then other kinds of developmental forces take shape. Well, we often think about nurture as something that might come a little bit later in brain development as the developing nervous system acquires the capacity for sensory experience and motor behavior. nurture can be thought of as environmental interactions, that is, experience dependent modulation of brain activity. There is brain activity going on at later stages in development once synapses begin to form and that activity is endogenous that is, it isn't necessarily reflecting the interactions of sensory receptors with stimuli in the environment. But increasingly, as the brain does develop, and certainly in postnatal life, a topic we'll come to in a later tutorial, the experience of the infant becomes an important shaper of ongoing development of the brain. So, we can think of nurture then, as environmental interactions of the developing brain, and obviously, when we consider genetics specification in sensory motor experience, we recognize that these factors interact. Well, until fairly recently, I probably would have been ready to move on at that point, but thanks to some wonderful collaborators that I've worked with over the last few years who come from a very different discipline, my collaborators, my friends they're actually theoretical physicists, and they've helped me understand that there's really a third major force in brain development that biologists ought to confront. And so, I've been happy to be educated and to really embrace this, this idea, and actually make it part of my research program. And that is to recognize that self organization is a very important force that shapes, that developments and the maturation of circuitry in the central nervous system. So what do I mean by self-organization? Well, self-organization, reflects the interactions of one cell to another, or many cells with respect to their neighborhood environments, and these interactions are mediated via activity based mechanisms. So, self-organization reflects the dynamical systems property of the developing brain. So, as systems form synaptic connections and they acquire the capacity to generate electrical signals and activity now becomes possible. Self-organization begins to shape the distribution of synaptic connections and, and axonal arbors, and the structure, what we call the functional architecture of neural networks. And I, and I, I've been slow to come to appreciate this concept because, until fairly recently, it hasn't really been possible to apply quantitative tools to characterize the organization of circuitry in the brain. But, now that we can do so, it's becoming, really quite compelling, I think, that the structure and the form and the precision of synaptic connections that we see in neural networks, is, is far greater than what can be accounted for from the genome, from genetic specification and we've done some experiments. And others, I think would concur that the degree of specification, of circuitry in the brain, couldn't possibly be instructed by a sensorimotor experience. So there must be an additional force, additional factor at play and that additional factor is self-organization. And so, self organization interacts with sensorimotor experience, it interacts with, genetically encoded mechanisms, and together, these 3 forces shape brain development. Now, as you might imagine, as these forces interact, there's opportunity, unfortunately, for things to go awry. Well, there are various ways in which these basic mechanisms of development can go awry in brain development. There can be mutations of genes that affect how, these genetic instructions are read out, how the genes are transcribed and how the messenger RNA molecules are translated into proteins and then how those proteins are actually processed and inserted where ever there functional role happens to require their presence. there are also, interactions among cells, that are mediated via these activity based mechanisms, that are responsible for self-organizing networks in the brain. And, well, self-organization seems to be remarkably robust against perturbations. One can imagine that the self organization of the brain might be forced into some different, kind of state or some different kind of dynamical system depending upon the interactions, perhaps, with molecules present in the environment that might effect how genetic instructions are played out. And then, lastly, one can imagine that sensory motor experience could be important in later stages of brain development and indeed, perhaps across the life-span as the experiences of the body begin to feedback upon the structure and function of the human brain. And, I think what we've learned from a variety of, of sources is that sensory motor experience can cut both ways. It can be beneficial. It can promote the maturation of the nervous system or it can be detrimental. It can reinforce functional impairment. Well, these are topics that I want to progressively unfold, but I, I do want to get them out there in front of you as we begin this consideration of the development of the nervous system and how the nervous system changes across the life span. Alright, so, what I'd like to do now is talk about the early stages of the formation of the nervous system which will largely reflect the expression of genetic specification in the developing brain.
