In humans and mice, mutations in Hoxa13 cause malformation of limb and genitourinary (GU) regions. In males, one of the most common GU malformations associated with loss of Hoxa13 function is hypospadia,a condition defined by the poor growth and closure of the urethra and glans penis. By examining early signaling in the developing mouse genital tubercle,we show that Hoxa13 is essential for normal expression of Fgf8 and Bmp7 in the urethral plate epithelium. In Hoxa13GFP-mutant mice, hypospadias occur as a result of the combined loss of Fgf8 and Bmp7 expression in the urethral plate epithelium, as well as the ectopic expression of noggin(Nog) in the flanking mesenchyme. In vitro supplementation with Fgf8 restored proliferation in homozygous mutants to wild-type levels, suggesting that Fgf8 is sufficient to direct early proliferation of the developing genital tubercle. However, the closure defects of the distal urethra and glans can be attributed to a loss of apoptosis in the urethra,which is consistent with reduced Bmp7 expression in this region. Mice mutant for Hoxa13 also exhibit changes in androgen receptor expression, providing a developmental link between Hoxa13-associated hypospadias and those produced by antagonists to androgen signaling. Finally,a novel role for Hoxa13 in the vascularization of the glans penis is also identified.
SummaryHOXA13 regulates the expression of bone morphogenetic proteins 2 and 7 to control distal limb morphogenesis
In the United States, Japan, United Kingdom, and Sweden, birth defects affecting the growth and development of the genitourinary (GU) regions are becoming increasingly prevalent, with incidences ranging as high as 1 in 125 live births. To understand the basis for these malformations, scientists have begun to examine the function of developmental genes in GU tissues. At the forefront of these investigations are studies examining the role of the 5' HOX proteins during the formation of the GU region. In this report we discuss what is known about HOXA13 and HOXD13 function during GU development, highlighting some of the cellular and molecular mechanisms controlled by these proteins during the GU formation. Finally, the translational benefits of identifying HOX target genes are discussed; first to explain the prevalence of some GU defects as well as a mechanism to facilitate their prevention in the birth population.
Habitat loss and degradation due to agricultural intensification and urbanization are key threats facing wild pollinators, especially bees. However, data on the distribution and abundance of most of the world's 20,000+ bee species is lacking, making it difficult to assess the effects of anthropogenic disturbance through time. Moreover, there are geographic biases in the study of bees creating gaps in our understanding of species distributions and regional patterns of diversity. Research efforts are often focused around cities or field stations associated with universities and other research institutions. In this perspectives paper, we provide examples of geographic bias in knowledge regarding bee species distributions using recently collected data from Michigan and Colorado, USA-two states with published species checklists. We illustrate how a limited sampling effort can advance knowledge about bee species distributions, yielding species occurrence records at local and regional scales. Given the implications of geographic biases, we recommend future research efforts focus on poorly sampled geographic regions, especially those affected by anthropogenic disturbance, in order to expand our understanding of human impacts on wild bee species. Sampling across a broader geographic area will provide critical information for taxonomy and predictive models of bee species distributions and diversity. We encourage researchers to plan future studies with consideration of strategies to avoid oversampling local bee populations, the taxonomic expertise required to identify specimens, and resources necessary to voucher specimens.
To gain insight into the coordination of gene expression profiles during forelimb and hindlimb differentiation, a transcriptome analysis of mouse embryonic autopod tissues was performed using Affymetrix Murine Gene Chips (MOE-430). Forty-four transcripts with expression differences higher than 2-fold (T test, P <0.05) were detected between forelimb and hindlimb tissues including 38 new transcripts such as Rdh10, Frzb, Tbx18, and Hip that exhibit differential limb expression. A comparison of gene expression profiles in the forelimb, hindlimb, and brain revealed 24 limb-signature genes whose expression was significantly enriched in limb autopod versus brain tissue (fold change >2, P < 0.05). Interestingly, the genes exhibiting enrichment in the developing autopod also segregated into significant fore-and hindlimbspecific clusters (P < 0.05) suggesting that by E 12.5, unique gene combinations are being used during the differentiation of each autopod type. Developmental Dynamics 234:74 -89, 2005.
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