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The Himalaya are among the youngest and highest mountains in the world, but the exact timing of their uplift and origins of their biodiversity are still in debate. The Himalayan region is a relatively small area but with exceptional diversity and endemism. One common hypothesis to explain the rich montane diversity is uplift-driven diversification–that orogeny creates conditions favoring rapid in situ speciation of resident lineages. We test this hypothesis in the Himalayan region using amphibians and reptiles, two environmental sensitive vertebrate groups. In addition, analysis of diversification of the herpetofauna provides an independent source of information to test competing geological hypotheses of Himalayan orogenesis. We conclude that the origins of the Himalayan herpetofauna date to the early Paleocene, but that diversification of most groups was concentrated in the Miocene. There was an increase in both rates and modes of diversification during the early to middle Miocene, together with regional interchange (dispersal) between the Himalaya and adjacent regions. Our analyses support a recently proposed stepwise geological model of Himalayan uplift beginning in the Paleocene, with a subsequent rapid increase of uplifting during the Miocene, finally give rise to the intensification of the modern South Asia Monsoon.

The pathogenesis of glomerular scarring is multifactional; recent evidence suggests that transforming growth factor beta (TGF beta), a pleiotropic cicatricial mediator, may promote mesangial sclerosis by enhancing the production of extracellular matrix proteins. We studied the effect of TGF beta 1 and TFG beta 2 on collagen type IV and fibronectin (FN) synthesis in human glomerular mesangial cells in culture (GMC). Two hours after addition of TGF beta, an up to twofold increase in abundance of collagen type IV mRNA was found, which further increased up to fivefold within 24 h. Addition of cycloheximide did not inhibit the TGF beta effect, but caused by itself an up to twofold increase in the abundance of collagen type IV mRNA after 2 h. Together with collagen mRNA, the mRNA for FN and for platelet-derived growth factor (PDGF) was also enhanced. PDGF was found to enhance abundance of the collagen type IV and fibronectin mRNA in GMC. A neutralizing antibody to PDGF or a PDGF-antisense oligonucleotide partly inhibited the TGF beta-induced increase of collagen type IV mRNA, suggesting that TGF beta can affect the collagen type IV synthesis not only directly but also indirectly via the synthesis of PDGF.

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The number and self-renewal capacity of hematopoietic stem cells (HSCs) are tightly regulated at different developmental stages. Many pathways have been implicated in regulating HSC development in cell autonomous manners; however, it remains unclear how HSCs sense and integrate developmental cues. In this study, we identified an extrinsic mechanism by which HSC number and functions are regulated during mouse puberty. We found that the HSC number in postnatal bone marrow reached homeostasis at 4 weeks after birth. Luteinizing hormone, but not downstream sex hormones, was involved in regulating HSC homeostasis during this period. Expression of luteinizing hormone receptor (Lhcgr) is highly restricted in HSCs and multipotent progenitor cells in the hematopoietic hierarchy. When Lhcgr was deleted, HSCs continued to expand even after 4 weeks after birth, leading to abnormally elevated hematopoiesis and leukocytosis. In a murine acute myeloid leukemia model, leukemia development was significantly accelerated upon Lhcgr deletion. Together, our work reveals an extrinsic counting mechanism that restricts HSC expansion during development and is physiologically important for maintaining normal hematopoiesis and inhibiting leukemogenesis.

Hematopoietic stem cells (HSCs) and skeletal stem cells (SSCs) cohabit in the bone marrow. KITL (C-KIT ligand) from LEPR + adult bone marrow stromal cells is pivotal for HSC maintenance. In contrast, it remains unclear whether KITL/C-KIT signaling also regulates SSCs.Here, we lineage traced C-KIT + cells and found that C-KIT was expressed by fetal, but not postnatal skeletal progenitors. Fetal C-KIT + cells gave rise to 20% of LEPR + stromal cells in adult bone marrow, forming nearly half of all osteoblasts. Disruption of mTOR signaling in fetal C-KIT + cells impaired bone formation. Notably, conditional deletion of Kitl from PRX1 + fetal bone marrow stromal cells, but not LEPR + adult bone marrow stromal cells, significantly increased bone formation. Thus, our work identified C-KIT + skeletal progenitors as an important source of bones formed during development.

Recent studies have highlighted the underestimated diversity of the genus Diploderma Hallowell, 1861 in the Hengduan Mountain Region in Southwest China, but much of the region remains poorly surveyed for reptile diversity. In this study we describe two new species of Diploderma from the upper Jinsha and middle Yalong River Valley, based on evaluations of morphological, genetic, and distribution data. The two new species are morphologically most similar to D. angustelinea and D. vela, but they can be diagnosed from both recognized taxa and all remaining congeners by a suite of morphological features, particularly the distinct coloration of gular spots. Additionally, both new species either render other recognized species paraphyletic or are allopatric with respect to their morphologically similar congeners. Furthermore, we rediscover D. brevicaudum in the wild for the first time, which was known from historical museum specimens only. We estimate the phylogenetic position of D. brevicaudum within the genus Diploderma based on mitochondrial genealogy, and we provide an expanded diagnosis and comparisons against closely related congeners and provide a detailed description of coloration in life based on newly collected specimens. Our discoveries of the new Diploderma species further highlight the urgent conservation needs of the currently neglected hot-dry valley ecosystems in the Hengduan Mountain Region of China.