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Loss of Hox5 function results in myofibroblast mislocalization and distal lung matrix defects during postnatal development

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Science China(Life Sciences) 2018年第9期61卷 1030-1038页

作者： steven M.hrycaj Leilani Marty-Santos ANDrew J.Rasky Nicholas W.Lukacs Deneen M.Wellik Department of Internal Medicine Division of Molecular Medicine and Genetics University of Michigan Department of Pathology University of Michigan Department of Cell and Developmental Biology University of Michigan

Alveologenesis is the final stage of lung development and is responsible for the formation of the principle gas exchange units called alveoli. The lung mesenchyme, in particular the alveolar myofibroblasts, are drivers of alveolar development, however,few key regulators that govern the proper distribution and behavior of these cells in the distal lung during alveologenesis have been identified. While Hox5 triple mutants(Hox5 aabbcc) exhibit neonatal lethality, four-allele, compound mutant mice(Hox5 AabbCc) are born in Mendelian ratios and are phenotypically normal at birth. However, they exhibit defects in alveologenesis characterized by a BPD-like phenotype by early postnatal stages that becomes more pronounced at adult stages. Invasive pulmonary functional analyses demonstrate significant increases in total lung volume and compliance and a decrease in elastance in Hox5 compound mutants. SMA+ myofibroblasts in the distal lung are distributed abnormally during peak stages of alveologenesis and aggregate, resulting in the formation of a disrupted elastin network. Examination of other key components of the distal lung ECM, as well as other epithelial cells and lipofibroblasts reveal no differences in distribution. Collectively, these data indicate that Hox5 genes play a critical role in alveolar development by governing the proper cellular behavior of myofibroblasts during alveologenesis.

关键词： Hox5 alveologenesis alveolar myofibroblasts lung ECM postnatal lung development

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Over-expression of Ultrabithorax alters embryonic body plan and wing patterns in the butterfly Bicyclus anynana

Over-expression of Ultrabithorax alters embryonic body plan ...

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第十二届家（柞）蚕遗传育种暨良种繁育学术研讨会

作者： Xiaoling Tong steven hrycaj Ondrej Podlaha Aleksandar Popadic Antónia Monteiro Department of Ecology and Evolutionary Biology Yale University State Key Laboratory of Silkworm Genome Biology Southwest University Department of Biological Sciences Wayne State University Department of Biological Sciences National University of Singapore

In insects, forewings and hindwings usually have different shapes, sizes, and color patterns. A variety of RNAi experiments across insect species have shown that the hox gene Ultrabithorax（Ubx） is necessary to promote hindwing identity. However, it remains unclear whether Ubx is sufficient to confer hindwing fate to forewings across insects. Here, we address this question by over-expressing Ubx in the butterfly Bicyclus anynana using a heat-shock promoter. Ubx whole-body over-expression during embryonic and larvae development led to body plan changes in larvae but to mere quantitative changes to adult morphology, respectively. Embryonic heat-shocks led to fused segments, loss of thoracic and abdominal limbs, and transformation of head limbs to larger appendages. Larval heat-shocks led to reduced eyespot size in the expected homeotic direction, but neither additional eyespots nor wing shape changes were observed in forewings as expected of a homeotic transformation. Interestingly, Ubx was found to be expressed in a novel, non-characteristic domain – in the hindwing eyespot centers. Furthermore, ectopic expression of Ubx on the pupal wing activated the eyespot-associated genes spalt and Distal-less, known to be directly repressed by Ubx in the fly’s haltere and leg primordia, respectively, and led to the differentiation of black wing scales. These results suggest that Ubx has been co-opted into a novel eyespot gene regulatory network, and that it is capable of activating black pigmentation in butterflies.

关键词： Ultrabithorax Over-expression Homeotic transformation Wing Eyespot Bicyclus anynana

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