Notochord morphogenesis in mice: Current understanding & open questions

Abstract

The notochord is the structure which defines chordates. It is a rod-like mesodermal structure that runs the anterior-posterior length of the embryo, adjacent to the ventral neural tube. The notochord plays a critical role in embryonic tissue patterning, for example the dorsal-ventral patterning of the neural tube. The cells that will come to form the notochord are specified at gastrulation. Axial mesodermal cells arising at the anterior primitive streak migrate anteriorly as the precursors of the notochord and populate the notochordal plate. Interestingly, even though a lot of interest has centered on investigating the functional and structural roles of the notochord, we still have a very rudimentary understanding of notochord morphogenesis. The events driving the formation of the notochord are rapid, taking place over the period of approximately a day in mice. In this commentary we provide an overview of our current understanding of mouse notochord morphogenesis, from the initial specification of axial mesendodermal cells at the primitive streak, the emergence of these cells at the midline on the surface of the embryo, to their submergence and organization of the stereotypically positioned notochord. We will also discuss some key open questions.

Pcdh18a-positive tip cells instruct notochord formation in zebrafish

“…Although our data does not exclude the possibility that the Pcdh18a positive NTC cells present a signal for the notochord cells to direct the cellular rearrangement in the trailing central mesoderm, we suggest that tension is the active agent. An additional hypothesis suggests that the two mesodermal wings push the notochordal plate and help to generate the rod-shaped structure of the notochord [41]. Our data suggest that blockade of Pcdh18a function uncouples partially the cell migration events in the axial mesoderm from the events in the LPM (Figure 1D; Supplementary figure 4B,C).…”

Understanding the Mechanobiology of Early Mammalian Development through Bioengineered Models

“…Regardless, while both the mouse and human micropattern platforms described above are perfect examples of the value of engineering approaches to development, in vivo cell fate specification and morphogenesis are heavily dependent on the 3D context of the developing embryo. In vivo development involves folding of tissues (e.g., neural, gut, or heart tube development) (Ivanovitch et al, 2017;Nikolopoulou et al, 2017;Spence et al, 2011), tissue migration and intercalation (e.g., gastrulation, notochord morphogenesis; Balmer et al, 2016;Rivera-Pé rez and Hadjantonakis, 2014;Viotti et al, 2014), and compartmentalization of soluble signals and their receptors (Zhang et al, 2018b). Understandably, these are features that cannot all be recapitulated by monolayer systems.…”

Mechanistic insights from the LHX1‐driven molecular network in building the embryonic head

“…At the completion of gastrulation, three germ layers are formed: the ectoderm for the skin and nervous system; the mesoderm for the skeleton, muscles and the circulatory system, and the endoderm for the gut and epithelial tissues (Williams & Solnica-Krezel, 2017). By the late-streak stage, Lhx1 expression is confined to the axial mesendoderm (the midline structure underneath the neural plate; Balmer, Nowotschin, & Hadjantonakis, 2016;Robb & Tam, 2004), the prechordal plate (derived from the gastrula organizer, Kinder, Tsang, Wakamiya, et al, 2001) and the anterior definitive endoderm. In the mid-streak embryo, expression can be seen in the entire AVE as well as the mesoderm extending anteriorly from the primitive streak.…”

“…In the mid-streak embryo, expression can be seen in the entire AVE as well as the mesoderm extending anteriorly from the primitive streak. By the late-streak stage, Lhx1 expression is confined to the axial mesendoderm (the midline structure underneath the neural plate; Balmer, Nowotschin, & Hadjantonakis, 2016;Robb & Tam, 2004), the prechordal plate (derived from the gastrula organizer, Kinder, Tsang, Wakamiya, et al, 2001) and the anterior definitive endoderm. Following gastrulation, in early head fold embryos, Lhx1 is expressed in the presumptive lateral mesoderm as well as the node (Barnes et al, 1994) before becoming more specified in the developing central nervous system and the nephrogenic tissues during organogenesis (Fujii et al, 1994).…”