Regionalized differentiation of CRH, TRH, and GHRH peptidergic neurons in the mouse hypothalamus

Abstract

According to the updated prosomeric model, the hypothalamus is subdivided rostrocaudally into terminal and peduncular parts, and dorsoventrally into alar, basal, and floor longitudinal zones. In this context, we examined the ontogeny of peptidergic cell populations expressing Crh, Trh, and Ghrh mRNAs in the mouse hypothalamus, comparing their distribution relative to the major progenitor domains characterized by molecular markers such as Otp, Sim1, Dlx5, Arx, Gsh1, and Nkx2.1. All three neuronal types originate mainly in the peduncular paraventricular domain and less importantly at the terminal paraventricular domain; both are characteristic alar Otp/Sim1-positive areas. Trh and Ghrh cells appeared specifically at the ventral subdomain of the cited areas after E10.5. Additional Ghrh cells emerged separately at the tuberal arcuate area, characterized by Nkx2.1 expression. Crh-positive cells emerged instead in the central part of the peduncular paraventricular domain at E13.5 and remained there. In contrast, as development progresses (E13.5–E18.5) many alar Ghrh and Trh cells translocate into the alar subparaventricular area, and often also into underlying basal neighborhoods expressing Nkx2.1 and/or Dlx5, such as the tuberal and retrotuberal areas, becoming partly or totally depleted at the original birth sites. Our data correlate a topologic map of molecularly defined hypothalamic progenitor areas with three types of specific neurons, each with restricted spatial origins and differential migratory behavior during prenatal hypothalamic development. The study may be useful for detailed causal analysis of the respective differential specification mechanisms. The postulated migrations also contribute to our understanding of adult hypothalamic complexity.

The Shark Alar Hypothalamus: Molecular Characterization of Prosomeric Subdivisions and Evolutionary Trends

“…In this territory, Otp expression co-distributes with that of Pax6 , Neurog2 , Lhx5 or Tbr1 genes (Stoykova et al, 1996; Medina, 2008; Abellán et al, 2010; Osório et al, 2010; Puelles et al, 2012; Ferrán et al, 2015) among others. Restricted expression patterns and certain progenitor subdomains led the authors of the model to divide the Pa into terminal or peduncular ( Figure 6A ; TPa, PPa; respectively) and different dorso-ventral subdomains (Morales-Delgado et al, 2011, 2014; Puelles et al, 2012; Ferrán et al, 2015; Puelles and Rubenstein, 2015). Moreover, the course of ascending tracts to the telencephalon through the rostral-most portion of the peduncular hypothalamus supports the existence of rostro-caudal subdivisions (Puelles et al, 2012; Puelles and Rubenstein, 2015).…”

“…In the mouse, tangential migrations involving the hypothalamus as source and/or recipient territory have been characterized by means of immunohistochemistry, autoradiography and ISH techniques (Morales-Delgado et al, 2011; Puelles et al, 2012; Morales-Delgado et al, 2014; Croizier et al, 2015; Díaz et al, 2015). The study of some of these intra-hypothalamic migrations led to the identification of three dorso-ventral progenitor subdomains (with their respective rostro-caudal subdivisions) in the Pa of the mouse (Morales-Delgado et al, 2011, 2014; Puelles et al, 2012).…”

“…The study of some of these intra-hypothalamic migrations led to the identification of three dorso-ventral progenitor subdomains (with their respective rostro-caudal subdivisions) in the Pa of the mouse (Morales-Delgado et al, 2011, 2014; Puelles et al, 2012). Furthermore, tangentially migrated cells derived from the Pa have been also described as contributing to extra-hypothalamic territories such as the amygdala (García-Moreno et al, 2010).…”

“…As a result, in the alar plate the hypothalamus presents at least four progenitor subdomains (from rostral to caudal and dorsal to ventral): terminal and peduncular paraventricular area (TPa, PPa; respectively), terminal and peduncular subparaventricular area (TSPa, PSPa; respectively). Further dorso-ventral subdivisions have also been proposed (Morales-Delgado et al, 2011, 2014; Puelles et al, 2012; Díaz et al, 2015; Ferrán et al, 2015; Puelles and Rubenstein, 2015). The relationships among these domains and hypothalamic nuclei have been pointed out: the TPa/PPa domain gives rise to magnocellular and parvocellular neurosecretory populations of the supraopto-paraventricular complex; the TSPa/PSPa domain will form mainly the suprachiasmatic nucleus, the anterior hypothalamic nucleus, and the subparaventricular zone, while the basal hypothalamus gives rise to classical tuberal and mamillary derivatives (Morales-Delgado et al, 2011; Puelles et al, 2012; Herget et al, 2014; Herget and Ryu, 2015).…”

Molecular regulation of hypothalamic development and physiological functions

“…These nuclei are the major developmental centers of the neuroendocrine system, where many endocrine progenitors are produced and then migrate to other brain sites [104–106]. …”