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      Ontogenetic Distribution of the Transcription Factor Nkx2.2 in the Developing Forebrain of Xenopus Laevis

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          Abstract

          The expression of the Nkx2.2 gene is involved in the organization of the alar-basal boundary in the forebrain of vertebrates. Its expression in different diencephalic and telencephalic regions, helped to define distinct progenitor domains in mouse and chick. Here we investigated the pattern of Nkx2.2 protein distribution throughout the development of the forebrain of the anuran amphibian, Xenopus laevis. We used immunohistochemical and in situ hybridization techniques for its detection in combination with other essential territorial markers in the forebrain. No expression was observed in the telencephalon. In the alar hypothalamus, Nkx2.2 positive cells were scattered in the suprachiasmatic territory, but also in the supraopto-paraventricular area, as defined by the expression of the transcription factor Orthopedia (Otp) and the lack of xDll4. In the basal hypothalamus Nkx2.2 expressing cells were localized in the tuberal region, with the exception of the arcuate nucleus, rich in Otp expressing cells. In the diencephalon it was expressed in all three prosomeres (P1–P3) and not in the zona limitans intrathalamica. The presence of Nkx2.2 expressing cells in P3 was restricted to the alar portion, as well as in prosomere P2, whereas in P1 the Nkx2.2 expressing cells were located in the basal plate and identified the alar/basal boundary. These results showed that Nkx2.2 and Sonic hedgehog are expressed in parallel adjacent stripes along the anterior–posterior axis. The results of this study showed a conserved distribution pattern of Nkx2.2 among vertebrates, crucial to recognize subdivisions that are otherwise indistinct, and supported the relevance of this transcription factor in the organization of the forebrain, particularly in the delineation of the alar/basal boundary of the forebrain.

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          Pallial and subpallial derivatives in the embryonic chick and mouse telencephalon, traced by the expression of the genes Dlx-2, Emx-1, Nkx-2.1, Pax-6, and Tbr-1.

          Pallial and subpallial morphological subdivisions of the developing chicken telencephalon were examined by means of gene markers, compared with their expression pattern in the mouse. Nested expression domains of the genes Dlx-2 and Nkx-2.1, plus Pax-6-expressing migrated cells, are characteristic for the mouse subpallium. The genes Pax-6, Tbr-1, and Emx-1 are expressed in the pallium. The pallio-subpallial boundary lies at the interface between the Tbr-1 and Dlx-2 expression domains. Differences in the expression topography of Tbr-1 and Emx-1 suggest the existence of a novel "ventral pallium" subdivision, which is an Emx-1-negative pallial territory intercalated between the striatum and the lateral pallium. Its derivatives in the mouse belong to the claustroamygdaloid complex. Chicken genes homologous to these mouse genes are expressed in topologically comparable patterns during development. The avian subpallium, called "paleostriatum," shows nested Dlx-2 and Nkx-2.1 domains and migrated Pax-6-positive neurons; the avian pallium expresses Pax-6, Tbr-1, and Emx-1 and also contains a distinct Emx-1-negative ventral pallium, formed by the massive domain confusingly called "neostriatum." These expression patterns extend into the septum and the archistriatum, as they do into the mouse septum and amygdala, suggesting that the concepts of pallium and subpallium can be extended to these areas. The similarity of such molecular profiles in the mouse and chicken pallium and subpallium points to common sets of causal determinants. These may underlie similar histogenetic specification processes and field homologies, including some comparable connectivity patterns. Copyright 2000 Wiley-Liss, Inc.
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            Forebrain gene expression domains and the evolving prosomeric model.

            The prosomeric model attributes morphological meaning to gene expression patterns and other data in the forebrain. It divides this territory into the same transverse segments (prosomeres) and longitudinal zones in all vertebrates. The axis and longitudinal zones of this model are widely accepted but controversy subsists about the number of prosomeres and their nature as segments. We describe difficulties encountered in establishing continuity between prosomeric limits postulated in the hypothalamus and intra-telencephalic limits. Such difficulties throw doubt on the intersegmental nature of these limits. We sketch a simplified model, in which the secondary prosencephalon (telencephalon plus hypothalamus) is a complex protosegment not subdivided into prosomeres, which exhibits patterning singularities. By contrast, we continue to postulate that prosomeres p1-p3 (i.e. the pretectum, thalamus and prethalamus) are the caudal forebrain.
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              The T/ebp null mouse: thyroid-specific enhancer-binding protein is essential for the organogenesis of the thyroid, lung, ventral forebrain, and pituitary.

              The thyroid-specific enhancer-binding protein (T/ebp) gene was disrupted by homologous recombination in embryonic stem cells to generate mice lacking T/EBP expression. Heterozygous animals developed normally, whereas mice homozygous for the disrupted gene were born dead and lacked the lung parenchyma. Instead, they had a rudimentary bronchial tree associated with an abnormal epithelium in their pleural cavities. Furthermore, the homozygous mice had no thyroid gland but had a normal parathyroid. In addition, extensive defects were found in the brain of the homozygous mice, especially in the ventral region of the forebrain. The entire pituitary, including the anterior, intermediate, and posterior pituitary, was also missing. In situ hybridization showed that the T/ebp gene is expressed in the normal thyroid, lung bronchial epithelium, and specific areas of the forebrain during early embryogenesis. These results establish that the expression of T/EBP, a transcription factor known to control thyroid-specific gene transcription, is also essential for organogenesis of the thyroid, lung, ventral forebrain, and pituitary.
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                Author and article information

                Journal
                Front Neuroanat
                Front. Neuroanat.
                Frontiers in Neuroanatomy
                Frontiers Research Foundation
                1662-5129
                29 December 2010
                02 March 2011
                2011
                : 5
                : 11
                Affiliations
                [1] 1simpleFaculty of Biology, Department of Cell Biology, University Complutense of Madrid Madrid, Spain
                Author notes

                Edited by: Fernando Martinez-Garcia, Universidad de Valencia, Spain

                Reviewed by: Loreta Medina, Universidad de Lleida, Spain; Isabel Rodríguez-Moldes, University of Santiago de Compostela, Spain

                *Correspondence: Nerea Moreno, Faculty of Biology, Department of Cell Biology, University Complutense of Madrid, C/José Antonio Novais 2, Madrid E-28040, Spain. e-mail: nerea@ 123456bio.ucm.es
                Article
                10.3389/fnana.2011.00011
                3049246
                21415915
                e7e0b76d-985f-4e4f-abac-037bac169e3f
                Copyright © 2011 Domínguez, González and Moreno.

                This is an open-access article subject to an exclusive license agreement between the authors and Frontiers Media SA, which permits unrestricted use, distribution, and reproduction in any medium, provided the original authors and source are credited.

                History
                : 05 November 2010
                : 16 February 2011
                Page count
                Figures: 6, Tables: 0, Equations: 0, References: 99, Pages: 13, Words: 10515
                Categories
                Neuroscience
                Original Research

                Neurosciences
                hypothalamus,in situ hybridization,thalamus,evolution,forebrain patterning,prosencephalon

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