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During ventral forebrain development, orthologs of the homeodomain transcription factor Nkx2.1 control patterning of hypothalamus, preoptic region, and ventral telencephalon. However, the relative contributions of Nkx2.1 and Nkx2.4 to prosencephalon development are poorly understood. Therefore, we analyzed functions of the previously uncharacterized nkx2.4-like zgc:171531 as well as of the presumed nkx2.1 orthologs nkx2.1a and nkx2.1b in zebrafish forebrain development. Our results show that zgc:171531 and nkx2.1a display overlapping expression patterns and a high sequence similarity. Together with a high degree of synteny conservation, these findings indicate that both these genes indeed are paralogs of nkx2.4. As a result, we name zgc:171531 now nkx2.4a, and changed the name of nkx2.1a to nkx2.4b, and of nkx2.1b to nkx2.1. In nkx2.1, nkx2.4a, and nkx2.4b triple morpholino knockdown (nkx2TKD) embryos we observed a loss of the rostral part of prosomere 3 and its derivative posterior tubercular and hypothalamic structures. Furthermore, there was a loss of rostral and intermediate hypothalamus, while a residual preoptic region still develops. The reduction of the ventral diencephalon was accompanied by a ventral expansion of the dorsally expressed pax6, revealing a dorsalization of the basal hypothalamus. Within the telencephalon we observed a loss of pallidal markers, while striatum and pallium are forming. At the neuronal level, nkx2TKD morphants lacked several neurosecretory neuron types, including avp, crh, and pomc expressing cells in the hypothalamus, but still form oxt neurons in the preoptic region. Our data reveals that, while nkx2.1, nkx2.4a, and nkx2.4b genes act partially redundant in hypothalamic development, nkx2.1 is specifically involved in the development of rostral ventral forebrain including the pallidum and preoptic regions, whereas nkx2.4a and nkx2.4b control the intermediate and caudal hypothalamus.
Pubmed ID: 25520628 RIS Download
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Online database for finding and analyzing syntenic regions across multiple genomes and measuring the extent of genome rearrangement using reversal distance as a measure.
View all literature mentionsModel organism database that serves as central repository and web-based resource for zebrafish genetic, genomic, phenotypic and developmental data. Data represented are derived from three primary sources: curation of zebrafish publications, individual research laboratories and collaborations with bioinformatics organizations. Data formats include text, images and graphical representations.Serves as primary community database resource for laboratory use of zebrafish. Developed and supports integrated zebrafish genetic, genomic, developmental and physiological information and link this information extensively to corresponding data in other model organism and human databases.
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