The Lim homeobox gene<i>Lhx2</i>is required for olfactory sensory neuron identity

Kolterud, Åsa; Alenius, Mattias; Carlsson, Leif; Bohm, Staffan

doi:10.1242/dev.01416

Cited by 87 publications

(79 citation statements)

References 36 publications

(52 reference statements)

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“…36 Thus, one could speculate that Lhx2 might inhibit the function of Gata-3, a master regulator of T cell differentiation. 37 Interestingly, both Lhx2 and Gata-3 have been implicated in stem cell maintenance in hair follicles 16,38 and in eye development, 14,39,40 suggesting a functional interaction between Lhx2 and Gata-3.…”

Section: Failure Of T-lymphoid Repopulation By Lhx2-transduced Hematomentioning

confidence: 99%

In vitro generation of HSC-like cells from murine ESCs/iPSCs by enforced expression of LIM-homeobox transcription factor Lhx2

Kitajima

Minehata

Sakimura

et al. 2011

Blood

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Section: Failure Of T-lymphoid Repopulation By Lhx2-transduced Hematomentioning

confidence: 99%

In vitro generation of HSC-like cells from murine ESCs/iPSCs by enforced expression of LIM-homeobox transcription factor Lhx2

Kitajima

Minehata

Sakimura

et al. 2011

Blood

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“…In this study, sensory epithelial cells at different maturation levels in the sensory neuronal lineage are detected by the expression of the following: Hes5-1 (Fior and Henrique, 2005), hereafter referred to as Hes5, which defines progenitor cells (Cau et al, 2000); Ngn1, which marks immediate neuronal precursors (Cau et al, 2002); members of the Hu class of RNA-binding proteins (HuC/D), which mark postmitotic neurons (Fornaro et al, 2003); and the transcription factor Lhx2, which identifies olfactory sensory neurons (Hirota and Mombaerts, 2004;Kolterud et al, 2004).…”

Section: Prospective Respiratory Epithelial Cells Express Msx1/2 and Id3mentioning

confidence: 99%

Opposing Fgf and Bmp activities regulate the specification of olfactory sensory and respiratory epithelial cell fates

et al. 2010

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SUMMARYThe olfactory sensory epithelium and the respiratory epithelium are derived from the olfactory placode. However, the molecular mechanisms regulating the differential specification of the sensory and the respiratory epithelium have remained undefined. To address this issue, we first identified Msx1/2 and Id3 as markers for respiratory epithelial cells by performing quail chick transplantation studies. Next, we established chick explant and intact chick embryo assays of sensory/respiratory epithelial cell differentiation and analyzed two mice mutants deleted of Bmpr1a;Bmpr1b or Fgfr1;Fgfr2 in the olfactory placode. In this study, we provide evidence that in both chick and mouse, Bmp signals promote respiratory epithelial character, whereas Fgf signals are required for the generation of sensory epithelial cells. Moreover, olfactory placodal cells can switch between sensory and respiratory epithelial cell fates in response to Fgf and Bmp activity, respectively. Our results provide evidence that Fgf activity suppresses and restricts the ability of Bmp signals to induce respiratory cell fate in the nasal epithelium. In addition, we show that in both chick and mouse the lack of Bmp or Fgf activity results in disturbed placodal invagination; however, the fate of cells in the remaining olfactory epithelium is independent of morphological movements related to invagination. In summary, we present a conserved mechanism in amniotes in which Bmp and Fgf signals act in an opposing manner to regulate the respiratory versus sensory epithelial cell fate decision.

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“…Lhx2 knockout mice do not express ORs, but since they also lack mature olfactory neurons, there is no evidence so far that this homeodomain protein is directly involved in OR gene expression (Hirota and Mombaerts 2004;Kolterud et al 2004). It is also possible that other homeodomain proteins than Lhx2 bind to the homeodomain sites in the OR gene promoters.…”

Section: Common or Gene Promoter Motifsmentioning

confidence: 99%

Identification of potential regulatory motifs in odorant receptor genes by analysis of promoter sequences

Michaloski¹,

Galante²,

Malnic³

2006

Genome Res.

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Mouse odorant receptors (ORs) are encoded by >1000 genes dispersed throughout the genome. Each olfactory neuron expresses one single OR gene, while the rest of the genes remain silent. The mechanisms underlying OR gene expression are poorly understood. Here, we investigated if OR genes share common cis-regulatory sequences in their promoter regions. We carried out a comprehensive analysis in which the upstream regions of a large number of OR genes were compared. First, using RLM-RACE, we generated cDNAs containing the complete 5Ј-untranslated regions (5Ј-UTRs) for a total number of 198 mouse OR genes. Then, we aligned these cDNA sequences to the mouse genome so that the 5Ј structure and transcription start sites (TSSs) of the OR genes could be precisely determined. Sequences upstream of the TSSs were retrieved and browsed for common elements. We found DNA sequence motifs that are overrepresented in the promoter regions of the OR genes. Most motifs resemble O/E-like sites and are preferentially localized within 200 bp upstream of the TSSs. Finally, we show that these motifs specifically interact with proteins extracted from nuclei prepared from the olfactory epithelium, but not from brain or liver. Our results show that the OR genes share common promoter elements. The present strategy should provide information on the role played by cis-regulatory sequences in OR gene regulation.

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The Lim homeobox geneLhx2is required for olfactory sensory neuron identity

Cited by 87 publications

References 36 publications

In vitro generation of HSC-like cells from murine ESCs/iPSCs by enforced expression of LIM-homeobox transcription factor Lhx2

In vitro generation of HSC-like cells from murine ESCs/iPSCs by enforced expression of LIM-homeobox transcription factor Lhx2

Opposing Fgf and Bmp activities regulate the specification of olfactory sensory and respiratory epithelial cell fates

Identification of potential regulatory motifs in odorant receptor genes by analysis of promoter sequences

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