<scp>LacZ‐reporter mapping of</scp><i>Dlx5</i>/<i>6</i><scp>expression and genoarchitectural analysis of the postnatal mouse prethalamus</scp>

Puelles, Luis; Dı́az, Carmen; Stühmer, Thorsten; Ferrán, José Luis; Torre, Margaret Martínez‐de la; Rubenstein, John L.R.

doi:10.1002/cne.24952

Cited by 30 publications

(87 citation statements)

References 245 publications

(734 reference statements)

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“…1 c, e, i), two positive groups of neurons in the caudal portion of the zona incerta (arrowhead in Fig. 1 g, i; Puelles et al 2020 ) and scattered positive cells in the periventricular mes-diencephalic basal plate (arrow on Fig. 1 e) draw our attention.…”

Section: Resultsmentioning

confidence: 78%

Neuronal tangential migration from Nkx2.1-positive hypothalamus

et al. 2020

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During the development of the central nervous system, the immature neurons suffer different migration processes. It is well known that Nkx2.1-positive ventricular layer give rise to critical tangential migrations into different regions of the developing forebrain. Our aim was to study this phenomenon in the hypothalamic region. With this purpose, we used a transgenic mouse line that expresses the tdTomato reporter driven by the promotor of Nkx2.1. Analysing the Nkx2.1-positive derivatives at E18.5, we found neural contributions to the prethalamic region, mainly in the zona incerta and in the mes-diencephalic tegmental region. We studied the developing hypothalamus along the embryonic period. From E10.5 we detected that the Nkx2.1 expression domain was narrower than the reporter distribution. Therefore, the Nkx2.1 expression fades in a great number of the early-born neurons from the Nkx2.1-positive territory. At the most caudal positive part, we detected a thin stream of positive neurons migrating caudally into the mes-diencephalic tegmental region using time-lapse experiments on open neural tube explants. Late in development, we found a second migratory stream into the prethalamic territory. All these tangentially migrated neurons developed a gabaergic phenotype. In summary, we have described the contribution of interneurons from the Nkx2.1-positive hypothalamic territory into two different rostrocaudal territories: the mes-diencephalic reticular formation through a caudal tangential migration and the prethalamic zona incerta complex through a dorsocaudal tangential migration.

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Section: Resultsmentioning

confidence: 78%

Neuronal tangential migration from Nkx2.1-positive hypothalamus

et al. 2020

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“…The prosomeric forebrain alar-basal longitudinal boundary roughly overlaps the longitudinal lineal expression of Nkx2.2 along the entire forebrain, now including the midbrain ( Figure 1C ; Shimamura et al, 1995 ; Rubenstein et al, 1998 ; Hauptmann et al, 2002 ; Domínguez et al, 2011 ; Puelles et al, 2012 , 2020 ; Nieuwenhuys and Puelles, 2016 ). The Nkx2.2 -positive band extends along the alar-basal boundary (a sign of equilibrium between ongoing floor-caused basal ventralization vs. roof-caused alar dorsalization, a fundamental patterning antagonism) before it can be detected by any other means.…”

Section: The Hypothalamus In a Historic Perspective: The Columnar Modmentioning

confidence: 84%

“…Expression of Plagl1 , Erbb4 , and Irx1 in the basal peduncular hypothalamus also stops caudally at the Di-Hy boundary. Moreover, the expression of members of the Dlx gene family in the prethalamus (alar rostral diencephalon) partially stops at the molecular hypothalamo-diencephalic boundary (Puelles et al, 2020 ).…”

Section: The Hypothalamus In the Updated Prosomeric Modelmentioning

confidence: 99%

Developmental Genes and Malformations in the Hypothalamus

Dı́az

Puelles

2020

Front. Neuroanat.

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The hypothalamus is a heterogeneous rostral forebrain region that regulates physiological processes essential for survival, energy metabolism, and reproduction, mainly mediated by the pituitary gland. In the updated prosomeric model, the hypothalamus represents the rostralmost forebrain, composed of two segmental regions (terminal and peduncular hypothalamus), which extend respectively into the non-evaginated preoptic telencephalon and the evaginated pallio-subpallial telencephalon. Complex genetic cascades of transcription factors and signaling molecules rule their development. Alterations of some of these molecular mechanisms acting during forebrain development are associated with more or less severe hypothalamic and pituitary dysfunctions, which may be associated with brain malformations such as holoprosencephaly or septo-optic dysplasia. Studies on transgenic mice with mutated genes encoding critical transcription factors implicated in hypothalamic-pituitary development are contributing to understanding the high clinical complexity of these pathologies. In this review article, we will analyze first the complex molecular genoarchitecture of the hypothalamus resulting from the activity of previous morphogenetic signaling centers and secondly some malformations related to alterations in genes implicated in the development of the hypothalamus.

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“…A recent research reported that cells in a thin superficial portion of the thalamus switched to GABAergic identity in Tcf7l2 -/embryos, shown by the colocalisation of Gad1 and Gbx2-driven tdTomato signal (Tran et al, 2020). However, the staining resolution does not allow concluding that the signals colocalised in the same cells; and according to the most recent research the origin of thalamic GABAergic cells may be assigned to prethalamic, rostral thalamic and even pretectal domains (Jager et al, 2016;Puelles et al, 2020). More importantly, normal pattern of Vglut2 and Gad1 expression in mice with the postnatally induced knockout of Tcf7l2 demonstrates that TCF7L2…”

Section: Development • Accepted Manuscriptmentioning

confidence: 99%

TCF7L2 regulates postmitotic differentiation programs and excitability patterns in the thalamus

et al. 2020

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Neuronal phenotypes are controlled by terminal selector transcription factors in invertebrates, but only a few examples of such regulators have been provided in vertebrates. We hypothesised that TCF7L2 regulates different stages of postmitotic differentiation in the thalamus, and functions as a thalamic terminal selector. To investigate this hypothesis, we used complete and conditional knockouts of Tcf7l2 in mice. The connectivity and clustering of neurons were disrupted in the thalamo-habenular region in Tcf7l2−/− embryos. The expression of subregional thalamic and habenular transcription factors was lost and region-specific cell migration and axon guidance genes were downregulated. In mice with a postnatal Tcf7l2 knockout, the induction of genes that confer thalamic terminal electrophysiological features was impaired. Many of these genes proved to be direct targets of TCF7L2. The role of TCF7L2 in terminal selection was functionally confirmed by impaired firing modes in thalamic neurons in the mutant mice. These data corroborate the existence of master regulators in the vertebrate brain that control stage-specific genetic programmes and regional subroutines, maintain regional transcriptional network during embryonic development, and induce terminal selection postnatally.

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LacZ‐reporter mapping ofDlx5/6expression and genoarchitectural analysis of the postnatal mouse prethalamus

Cited by 30 publications

References 245 publications

Neuronal tangential migration from Nkx2.1-positive hypothalamus

Neuronal tangential migration from Nkx2.1-positive hypothalamus

Developmental Genes and Malformations in the Hypothalamus

TCF7L2 regulates postmitotic differentiation programs and excitability patterns in the thalamus

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