Msx2 deficiency in mice causes pleiotropic defects in bone growth and ectodermal organ formation

The composite structure of the mammalian skull, which forms predominantly via intramembranous ossification, requires precise pre- and post-natal growth regulation of individual calvarial elements. Disturbances of this process frequently cause severe clinical manifestations in humans. Enhanced DNA binding by a mutant MSX2 homeodomain results in a gain of function and produces craniosynostosis in humans. Here we show that Msx2-deficient mice have defects of skull ossification and persistent calvarial foramen. This phenotype results from defective proliferation of osteoprogenitors at the osteogenic front during calvarial morphogenesis, and closely resembles that associated with human MSX2 haploinsufficiency in parietal foramina (PFM). Msx2-/- mice also have defects in endochondral bone formation. In the axial and appendicular skeleton, post-natal deficits in Pth/Pthrp receptor (Pthr) signalling and in expression of marker genes for bone differentiation indicate that Msx2 is required for both chondrogenesis and osteogenesis. Consistent with phenotypes associated with PFM, Msx2-mutant mice also display defective tooth, hair follicle and mammary gland development, and seizures, the latter accompanied by abnormal development of the cerebellum. Most Msx2-mutant phenotypes, including calvarial defects, are enhanced by genetic combination with Msx1 loss of function, indicating that Msx gene dosage can modify expression of the PFM phenotype. Our results provide a developmental basis for PFM and demonstrate that Msx2 is essential at multiple sites during organogenesis.     

番荔枝科糠秕鳞杜氏木群及其近缘种的修订(Ⅰ)——分种检索表及糠秕鳞杜氏木的描述(英文)

世界上至今报道的番荔枝科杜氏木属有约80种.糠秕鳞杜氏木群及其近缘种包含16种(现修订至12种),隶属于产热带南美洲的具有26种的杜氏木组.本文是作者经过详尽研究了存于美、英、瑞典、法、荷及巴西等国家25家以上标本馆的1500余份标本(包括每种的模式标本)以及花、果收藏品后对糠秕鳞杜氏本群及其近缘种作的修订.至于本群的形态术语,其附属物被大体上分成两类,即鳞斑和星状毛.次级叶脉可归成两大类,即“单型弯曲”对应“急弯曲”,花序以“与叶对生”和“假顶生”来表述.新定义的和稍微修改过的名词术语成功地用于描述中.文中对分类学历史作了简要讨论.给出了分种检索表以及对该群作为一个总体和对该群中分布最广显示出种下形态变异性活跃的最具变化性的种即糠秕鳞杜氏木作了描述.赫门多夫杜氏木(D.hemmendorffii)及乔安娜杜氏木(D.jonasiana)被归并作为糠秕鳞杜氏木(D.furfuraceea)的异名.     

番荔枝科糠秕鳞杜氏木群及其近缘种的修订(Ⅲ)——种的描述、分类定界及亲缘关系(英文)

本文是第一作者在荷兰鸟支大学系统植物学研究所进修期间完成的番茄枝科杜氏木属(Duguetia)中糠秕鳞杜氏木群及近缘种专著修订的第三部分.文中给出了属于糠秕鳞杜氏木群的下列四种:鳞斑杜氏木(D.lepidota)、芳香杜氏木(D.odorata)、光叶杜氏木(D.glabriuscula)、及披针叶杜氏木(D.lanceolata)的详尽形态描述、分类定界、地理分布、地方名、应用价值及相互亲缘关系.小叶披针叶杜氏木(D.lanceolata)var.parvifolia)被认为是披针叶杜氏木的极端变异,其分类等级不能被承认,芳香杜氏木不象R.E.Fries(1934.1959)认为那样与糠秕鳞杜氏木有直接亲缘,而是与鳞斑杜氏木亲缘关系极近.     

Genomic structure, evolutionary conservation and aniridia mutations in the human PAX6 gene.

Aniridia is a semidominant disorder in which development of the iris, lens, cornea and retina is disturbed. The mouse mutation Small eye (Sey), which has been proposed as a model for aniridia, results from defects in Pax-6, a gene containing paired-box and homeobox motifs that is specifically expressed in the developing eye and brain. To test the role of PAX6 in aniridia, we isolated human cDNA clones and determined the intron-exon structure of this gene. PAX6 spans 22 kilobases and is divided into 14 exons. Analysis of DNA from 10 unrelated aniridia patients revealed intragenic mutations in three familial and one sporadic case. These findings indicate that the human aniridia and murine Small eye phenotypes arise from homologous defects in PAX6.     

A physical map of the mouse genome

A physical map of a genome is an essential guide for navigation, allowing the location of any gene or other landmark in the chromosomal DNA. We have constructed a physical map of the mouse genome that contains 296 contigs of overlapping bacterial clones and 16,992 unique markers. The mouse contigs were aligned to the human genome sequence on the basis of 51,486 homology matches, thus enabling use of the conserved synteny (correspondence between chromosome blocks) of the two genomes to accelerate construction of the mouse map. The map provides a framework for assembly of whole-genome shotgun sequence data, and a tile path of clones for generation of the reference sequence. Definition of the human-mouse alignment at this level of resolution enables identification of a mouse clone that corresponds to almost any position in the human genome. The human sequence may be used to facilitate construction of other mammalian genome maps using the same strategy.     

Femtosecond X-ray protein nanocrystallography

X-ray crystallography provides the vast majority of macromolecular structures, but the success of the method relies on growing crystals of sufficient size. In conventional measurements, the necessary increase in X-ray dose to record data from crystals that are too small leads to extensive damage before a diffraction signal can be recorded. It is particularly challenging to obtain large, well-diffracting crystals of membrane proteins, for which fewer than 300 unique structures have been determined despite their importance in all living cells. Here we present a method for structure determination where single-crystal X-ray diffraction 'snapshots' are collected from a fully hydrated stream of nanocrystals using femtosecond pulses from a hard-X-ray free-electron laser, the Linac Coherent Light Source. We prove this concept with nanocrystals of photosystem I, one of the largest membrane protein complexes. More than 3,000,000 diffraction patterns were collected in this study, and a three-dimensional data set was assembled from individual photosystem I nanocrystals (～200?nm to 2?μm in size). We mitigate the problem of radiation damage in crystallography by using pulses briefer than the timescale of most damage processes. This offers a new approach to structure determination of macromolecules that do not yield crystals of sufficient size for studies using conventional radiation sources or are particularly sensitive to radiation damage.     

Protein arginine methylation: a prominent modification and its demethylation

Arginine methylation of histones is one mechanism of epigenetic regulation in eukaryotic cells. Methylarginines can also be found in non-histone proteins involved in various different processes in a cell. An enzyme family of nine protein arginine methyltransferases catalyses the addition of methyl groups on arginines of histone and non-histone proteins, resulting in either mono- or dimethylated-arginine residues. The reversibility of histone modifications is an essential feature of epigenetic regulation to respond to changes in environmental factors, signalling events, or metabolic alterations. Prominent histone modifications like lysine acetylation and lysine methylation are reversible. Enzyme family pairs have been identified, with each pair of lysine acetyltransferases/deacetylases and lysine methyltransferases/demethylases operating complementarily to generate or erase lysine modifications. Several analyses also indicate a reversible nature of arginine methylation, but the enzymes facilitating direct removal of methyl moieties from arginine residues in proteins have been discussed controversially. Differing reports have been seen for initially characterized putative candidates, like peptidyl arginine deiminase 4 or Jumonji-domain containing protein 6. Here, we review the most recent cellular, biochemical, and mass spectrometry work on arginine methylation and its reversible nature with a special focus on putative arginine demethylases, including the enzyme superfamily of Fe(II) and 2-oxoglutarate-dependent oxygenases.