Genoarchitecture of the Early Postmitotic Pretectum and the Role of Wnt Signaling in Shaping Pretectal Neurochemical Anatomy in Zebrafish

Abstract

The pretectum has a distinct nuclear arrangement and complex neurochemical anatomy. While previous genoarchitectural studies have described rostrocaudal and dorsoventral progenitor domains and subdomains in different species, the relationship between these early partitions and its later derivatives in the mature anatomy is less understood. The signals and transcription factors that control the establishment of pretectal anatomy are practically unknown. We investigated the possibility that some aspects of the development of pretectal divisions are controlled by Wnt signaling, focusing on the transitional stage between neurogenesis and histogenesis in zebrafish. Using several molecular markers and following the prosomeric model, we identified derivatives from each rostrocaudal pretectal progenitor domain and described the localization of gad1b-positive GABAergic and vglut2.2-positive glutamatergic cell clusters. We also attempted to relate these clusters to pretectal nuclei in the mature brain. Then, we examined the influence of Wnt signaling on the size of neurochemically distinctive pretectal areas, using a chemical inhibitor of the Wnt pathway and the CRISPR/Cas9 approach to knock out genes that encode the Wnt pathway mediators, Lef1 and Tcf7l2. The downregulation of the Wnt pathway led to a decrease in two GABAergic clusters and an expansion of a glutamatergic subregion in the maturing pretectum. This revealed an instructive role of the Wnt signal in the development of the pretectum during neurogenesis. The molecular anatomy presented here improves our understanding of pretectal development during early postmitotic stages and support the hypothesis that Wnt signaling is involved in shaping the neurochemical organization of the pretectum.

Genoarchitectonics of the larval zebrafish diencephalon

“…Regarding overall brain development, there is general congruence in the description of expression patterns in the 28 hpf embryonic brain (Brożko et al., 2022; Lauter et al., 2013) compared to the 6 dpf larval brain dealt with in the present report. Moreover, for at least three genes studied in detail, it has been demonstrated that a general continuation of expression is seen between larval and adult brain ( islet1 : Baeuml et al., 2019; shha : Wullimann & Umeasalugo, 2020; otpa : Eugenin von Bernhardi et al., 2022).…”

“…However, a possible violation of the prosomeric model (Puelles & Rubenstein, 1993) is seen in the so-called tail end of various alar P2 domains that seemingly deviate posteriorly into P1 (e.g., gbx2 and lhx9; see Figure 5i). This observation has been made before (Brożko et al, 2022;Lauter et al, 2013) and may be interpreted in two ways: the tail end of these expression domains, which otherwise characterize alar P2, represents in fact cells that express these "dorsal thalamic" genes but are a part of P1. Alternatively, this tail end of alar P2 domains in question transgresses the P2/P1 boundary and forms truly a wedge of P2 between alar and basal P1.…”

Expression Pattern of nos1 in the Developing Nervous System of Ray-Finned Fish

“…The prosomeric model was used to localize the main common landmarks of the central nervous system during development, main partitions of the brain, and postulate homologies. Following the prosomeric model, the positions of neural populations can be identified by specific gene expression patterns (neural genoarchitecture) [41,42]. Homologues' derivatives share the same topological position in the Bauplan, an aspect that gene expression patterns help clarify [28,[42][43][44][45].…”

“…Following the prosomeric model, the positions of neural populations can be identified by specific gene expression patterns (neural genoarchitecture) [41,42]. Homologues' derivatives share the same topological position in the Bauplan, an aspect that gene expression patterns help clarify [28,[42][43][44][45].…”

Transcriptional control of visual neural circuit development by GS homeobox 1

“…Retinorecipient cells within the Pr, thalamus, and TeO cluster based on their unique gene expression profiles that do not appear to change with loss of retinal input (Sherman et al, 2021). These findings and others suggest that genetic profiles are hard-wired in regions where RGC axons make connections and govern cellular mechanisms for the development and function of AFs (Baier, 2013;Brożko et al, 2022;Sherman et al, 2021). Due to identified changes in neuronal identity in the gsx1 mutant Pr, we looked to next assess the morphology of incoming RGC axons using Tg(atoh7:eGFP), a transgenic line that demarcates all RGCs and their axons with GFP expression (Poggi et al, 2005).…”