Neurogenetic Heterochrony in Chick, Lizard, and Rat Mapped with Wholemount Acetylcholinesterase and the Prosomeric Model

Abstract

In the developing brain, the phenomenon of neurogenesis is manifested heterotopically, that is, much the same neurogenetic steps occur at different places with a different timetable. This is due apparently to early molecular regionalization of the neural tube wall in the anteroposterior and dorsoventral dimensions, in a checkerboard pattern of more or less deformed quadrangular histogenetic areas. Their respective fate is apparently specified by a locally specific combination of active/repressed genes known as ‘molecular profile’. This leads to position-dependent differential control of proliferation, neurogenesis, differentiation, and other aspects, eventually in a heterochronic manner across adjacent areal units with sufficiently different molecular profiles. It is not known how fixed these heterochronic patterns are. We reexamined here comparatively early patterns of forebrain and hindbrain neurogenesis in a lizard (Lacerta gallotia galloti), a bird (the chick), and a mammal (the rat), as demonstrated by activation of acetylcholinesterase (AChE). This is an early marker of postmitotic neurons, which leaves unlabeled the neuroepithelial ventricular cells, so that we can examine cleared wholemounts of the reacted brains to have a birds-eye view of the emergent neuronal pattern at each stage. There is overall heterochrony between the basal and alar plates of the brain, a known fact, but, remarkably, heterochrony occurs even within the precocious basal plate among its final anteroposterior neuromeric subdivisions and their internal microzonal subdivisions. Some neuromeric units or microzones are precocious, while others follow suit without any specific spatial order or gradient; other similar neuromeric units remain retarded in the midst of quite advanced neighbors, though they do produce similar neurogenetic patterns at later stages. It was found that some details of such neuromeric heterochrony are species-specific, possibly related to differential morphogenetic properties. Given the molecular causal underpinning of the updated prosomeric model used here for interpretation, we comment on the close correlation between some genetic patterns and the observed AChE differentiation patterns.

Populational heterogeneity and partial migratory origin of the ventromedial hypothalamic nucleus: genoarchitectonic analysis in the mouse

“…Interpreting their data in terms of the columnar model, Aslanpour et al (2020b) identified a "rostrocaudal" gradient in VMH birthdates, which we translate topologically to the prosomeric model as a dorsoventral gradient. Presumably TuD neurogenesis precedes that of TuI, which is consistent with reported wholemount rat results using AChE as an early differentiation marker (Puelles et al 2015;Amat et al 2022). Accordingly, we deduce that our dorsal tuberal Nr5a1 and Nkx2.2 VMH cells would be born earlier (E10.5) than the ventral ones (E11.5), due to their origin in the more precocious TuD area.…”

“…The prosomeric hypothalamus consists of two prosomeres, hp2 and hp1, which represent its structure transversal to the axis of the forebrain (Fig. 1 ; the prosomeric axis is co-defined by the notochord, the floorplate, the alar-basal boundary and the roofplate as mutually parallel longitudinal reference landmarks lying at different dorsoventral levels; Puelles 2018 ; Amat et al 2022 ; the optic tract may be taken as another such reference; Puelles 2022 ). These two units are both hypothalamo-telencephalic in spatial range and contain respectively the terminal hypothalamus which extends into the non-evaginated preoptic telencephalic subpallium (THy in hp2; Fig.…”

“…Nkx2.2 is well known as an early longitudinal marker of the alar-basal boundary along the whole forebrain tagma (midbrain, diencephalon, and hypothalamus; note this is a basic token of the updated extended forebrain concept held within the prosomeric model; Puelles et al 2012 ; Puelles and Rubenstein 2015 ; Puelles 2018 ; Amat et al 2022 ). This lineal signal also appears bordering the spike of Shh expression that marks the transverse alar zona limitans intrathalamica (alar p3/p2 boundary), also known as the mid-diencephalic organizer (Puelles and Martínez 2013 ).…”

Dorsoventral Arrangement of Lateral Hypothalamus Populations in the Mouse Hypothalamus: a Prosomeric Genoarchitectonic Analysis

“…LH2 is the LH subregion associated with the periretromamillary (PRM) basal subdomain. This subdomain was first defined molecularly by Puelles et al [ 17 ] as associated with selective Otp and Sim1 basal plate signals, unrelated to alar expression domains of the same markers (see also [ 82 – 85 ].…”

Evolution of Developmental Timing as a Driving Force of Brain Diversity

“…In a descriptive tour de force, Amat et al [2022] present a comprehensive analysis of neurogenic trajectories in amniotes by examining histological samples of developing brains of lizards, chickens, and rats. By adopting a neuromeric framework of brain organization, wholemount acetylcholinesterase preparations -used as a marker of postmitotic neurons -are thoroughly examined between species and stages with a focus on the relative positions, trajectories, and functional boundaries along the rostro-caudal and basal-to-alar axes.…”