Regulation of size and scale in vertebrate spinal cord development

All vertebrates have a spinal cord with dimensions and shape specific to their species. Yet how species‐specific organ size and shape are achieved is a fundamental unresolved question in biology.

These processes are controlled by global tissue‐scale regulators, such as morphogen signaling gradients as well as mechanical forces. Current challenges in the field are to uncover how these tissue‐scale regulatory mechanisms are translated to the cellular and molecular level, and how regulation of distinct cellular processes gives rise to an overall defined size. Addressing these questions will help not only to achieve a better understanding of how size is controlled, but also of how tissue size is coordinated with the specification of pattern.

How organ size is determined during development is one of the most fundamental unresolved questions in biology.

The question of why elephants are bigger than mice has been asked many times, almost always accompanied by the surprise of how little we know about the answer

There is still much to be learned about the individual determinants of tissue growth—initial size, cell cycle progression, cell size and shape, and tissue anisotropy (see Box 1). The role of morphogen signaling, mechanics and other mechanisms in regulating these processes is poorly understood.

KEY QUESTIONS

  • The initial pool of progenitors that gives rise to the spinal cord, the changes in cell number driven by cell proliferation and cell loss, the cell sizes and shapes, and the anisotropy of tissue growth can affect the overall size and shape of the spinal cord. What is the contribution of each of these factors to spinal cord size in different species?

  • How do morphogens control the rates of cell proliferation, neuronal differentiation and apoptosis in the spinal cord? What are the molecular targets of morphogen signaling within the machineries that regulate these processes? How does the interpretation of morphogen signaling at the molecular level determine the tissue level dynamics of spinal cord growth?

  • How is the dynamics of neuronal differentiation controlled? How is neuronal differentiation molecularly linked to the control of cell cycle length and cell cycle progression? To what extent is the differentiation rate determined by the dynamics of cell intrinsic gene regulatory networks versus cell extrinsic factors?

  • How do progenitor cell sizes and shapes change during spinal cord development and how is this regulated?

  • How is the anisotropy of tissue growth controlled in the spinal cord? What is the role of mechanical forces versus biochemical signaling in this process?

  • How is spinal cord size sensed and corrected during development? What are the common and what are the distinct features of growth control systems in different species?

  • How is spinal cord pattern coordinated with its size? How do different species achieve pattern scaling between differently sized individuals?