The cytoskeletal mechanics of brain morphogenesis

Abstract

There is a functional device in embryonic ectodermal cells that we propose causes them to differentiate into either neuroepithelial or epidermal tissue during the process called primary neural induction. We call this apparatus the "cell state splitter." Its main components are the apical microfilament ring and the coplanar apical mat of microtubules, which exert forces in opposite radial directions. We analyze the mechanical interaction between these cytoskeletal components and show that they are in an unstable mechanical equilibrium. The role of the cell state splitter is thus to create a mechanical instability corresponding to the embryonic state of "competence" in an otherwise mechanically stable cell. When the equilibrium of the cell state splitter is disturbed so as to produce a slight contraction of the apical end, apical contraction continues and the distinctive columnar neuroepithelial cells are produced. A slight expansion from the equilibrium state, on the other hand, results in flattened epidermal cells. The calculated forces are consistent with the known constitutive and force-generating properties and morphology of microfilaments and microtubules, and with free tubulin concentrations. There are no free parameters in the analysis. The first cells to assume the neuroepithelial state lie over the notochord. Propagation of the neuroepithelial state (homoiogenetic induction) then proceeds via stretch-induced constriction of the apical microfilament rings, until a hemisphere is covered, at which point the high rate of change of the meridional stress component necessary for further propagation vanishes. The remaining cells are stretched somewhat by this process and become epidermis. A sharp boundary between the tissues is thus formed (explaining "compartmentalization" and the binary nature of differentiation in general). Normal induction apparently involves setup of the cell state splitters in all of the ectoderm cells, perhaps synchronously timed by global embryo tension. The initial transition of cells from the ectodermal to the neuroepithelial state begins at the notoplate, where cell attachments to the notochord may both cause basal actin deposition and significantly reduce the stress induced in the ectoderm by the global tension, biasing the notoplate cell state splitters toward the neuroepithelial state. Introduction of an organizer or other solid substrate (artificial inducer) elsewhere, to which ectodermal cells can adhere, may likewise have both of these effects. Differentiation to either epidermis or neuroepithelium is thus a mechanical event followed by the synthesis of specific proteins.(ABSTRACT TRUNCATED AT 400 WORDS)

The organelle of differentiation in embryos: the cell state splitter

“…[ 125 ]). We can infer then that it is not disassembled but instead becomes ever more tightly overlapping in a thickening and strengthening actin cable formation driven [ 126 ] by myosin 2, as we proposed for the cell state splitter [ 9 ]. Because the actin ring thickens this way, it is able to exert an increasing amount of force as it contracts Conversely, the force will decrease if the cell’s top (apical) diameter becomes larger and the ring is thinned.…”

“…We first discovered the cell state splitter in the ectoderm of the axolotl [ 9 ]. It has the three components: a microfilament ring [ 122 ], such as is common in epithelia [ 123 ]; a mat of microtubules at and parallel to the apical surface; and an intermediate filament ring (Fig.…”

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Fig. 5 The cell state splitter is an organelle predicted [ 9 ] and then at first observed at the apical end of ectoderm cells in axolotl embryos at early gastrulation [ 11 ]. It consists of an upper microfilament ring with an intermediate filament ring below it, subtended by a mat of microtubules.

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“…1 ) are linked to embryo form over time, i.e., to embryogenesis. The key to this is our prediction [ 9 ] and discovery [ 10 , 11 ] of the organelle of differentiation, a cytoskeletal apparatus we call the cell state splitter, that propagates differentiation waves from cell to cell as it initiates a step of differentiation within its cell. This review is excerpted from and elaborates on a book length exposition [ 12 ] (with permission of World Scientific Publishing).…”

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“…This type of structural approach provides information regarding spatial organization in the embryo, which may or may not be similar at different spatial scales. Scale-invariance is an important but understudied feature of early embryogenesis, and may exist in the early embryo as a self-regulating system of positional information (Lokeshwar & Nanjundiah, 1980/1981 or be due to the size independence of the geometry of differentiation waves (Gordon & Brodland, 1987, Gordon, 1999. It also provides empirical detail to a model of the cybernetic embryo (Stone & Gordon, 2017).…”