Anita Schuchardt

Bio: Anita Schuchardt is an academic researcher from University of Minnesota. The author has contributed to research in topics: Science education & Receptor tyrosine kinase. The author has an hindex of 13, co-authored 33 publications receiving 3104 citations. Previous affiliations of Anita Schuchardt include University of Pittsburgh & Columbia University.

Defects in the kidney and enteric nervous system of mice lacking the tyrosine kinase receptor Ret

Abstract: Receptor tyrosine kinases (RTKs) are cell-surface molecules that transduce signals for cell growth and differentiation. The RTK encoded by the c-ret proto-oncogene is rearranged and constitutively activated in a large proportion of thyroid papillary carcinomas, and germ-line point mutations in c-ret seem to be responsible for the dominantly inherited cancer syndromes multiple endocrine neoplasia (MEN) types 2A and B. The gene is expressed in the developing central and peripheral nervous systems (sensory, autonomic and enteric ganglia) and the excretory system (Wolffian duct and ureteric bud epithelium) of mice, indicating that it may play a role in normal development. Here we show that mice homozygous for a targeted mutation in c-ret develop to term, but die soon after birth, showing renal agenesis or severe dysgenesis, and lacking enteric neurons throughout the digestive tract. Ret is thus an essential component of a signalling pathway required for renal organogenesis and enteric neurogenesis.

Common origin and developmental dependence on c-ret of subsets of enteric and sympathetic neuroblasts.

Abstract: c-ret encodes a tyrosine kinase receptor that is necessary for normal development of the mammalian enteric nervous system. Germline mutations in c-ret lead to congenital megacolon in humans, while a loss-of-function allele (ret.k-) causes intestinal aganglionosis in mice. Here we examine in detail the function of c-ret during neurogenesis, as well as the lineage relationships among cell populations in the enteric nervous system and the sympathetic nervous system that are dependent on c-ret function. We report that, while the intestine of newborn ret.k- mice is devoid of enteric ganglia, the esophagus and stomach are only partially affected; furthermore, the superior cervical ganglion is absent, while more posterior sympathetic ganglia and the adrenal medulla are unaffected. Analysis of mutant embryos shows that the superior cervical ganglion anlage is present at E10.5, but absent by E12.5, suggesting that c-ret is required for the survival or proliferation of sympathetic neuroblasts. In situ hybridization studies, as well as direct labelling of cells with DiI, indicate that a common pool of neural crest cells derived from the postotic hindbrain normally gives rise to most of the enteric nervous system and the superior cervical ganglion, and is uniquely dependent on c-ret function for normal development. We term this the sympathoenteric lineage. In contrast, a distinct sympathoadrenal lineage derived from trunk neural crest forms the more posterior sympathetic ganglia, and also contributes to the foregut enteric nervous system. Overall, our studies reveal previously unknown complexities of cell lineage and genetic control mechanisms in the developing mammalian peripheral nervous system.

Renal agenesis and hypodysplasia in ret-k- mutant mice result from defects in ureteric bud development.

Abstract: The c-ret gene encodes a receptor tyrosine kinase that is expressed in the Wolffian duct and ureteric bud of the developing excretory system. Newborn mice homozygous for a mutation in c-ret displayed renal agenesis or severe hypodysplasia, suggesting a critical role for this gene in metanephric kidney development. To investigate the embryological basis of these defects, we characterized the early development of the excretory system in mutant homozygotes, and observed a range of defects in the formation, growth and branching of the ureteric bud, which account for the spectrum of renal defects seen at birth. Co-culture of isolated ureteric buds and metanephric mesenchyme show that the primary defect is intrinsic to the ureteric bud. While the mutant bud failed to respond to induction by wild-type mesenchyme, mutant mesenchyme was competent to induce the growth and branching of the wild-type bud. Furthermore, the mutant metanephric mesenchyme displayed a normal capacity to differentiate into nephric tubules when co-cultured with embryonic spinal cord. These findings suggest a model in which c-ret encodes the receptor for a (yet to be identified) factor produced by the metanephric mesenchyme, which mediates the inductive effects of this tissue upon the ureteric bud. This factor appears to stimulate the initial evagination of the ureteric bud from the Wolffian duct, as well as its subsequent growth and branching.

Distal ureter morphogenesis depends on epithelial cell remodeling mediated by vitamin A and Ret

Abstract: Distal ureter morphogenesis depends on epithelial cell remodeling mediated by vitamin A and Ret

Neurotrophins: roles in neuronal development and function.

Abstract: Neurotrophins regulate development, maintenance, and function of vertebrate nervous systems. Neurotrophins activate two different classes of receptors, the Trk family of receptor tyrosine kinases and p75NTR, a member of the TNF receptor superfamily. Through these, neurotrophins activate many signaling pathways, including those mediated by ras and members of the cdc-42/ras/rho G protein families, and the MAP kinase, PI-3 kinase, and Jun kinase cascades. During development, limiting amounts of neurotrophins function as survival factors to ensure a match between the number of surviving neurons and the requirement for appropriate target innervation. They also regulate cell fate decisions, axon growth, dendrite pruning, the patterning of innervation and the expression of proteins crucial for normal neuronal function, such as neurotransmitters and ion channels. These proteins also regulate many aspects of neural function. In the mature nervous system, they control synaptic function and synaptic plasticity, while continuing to modulate neuronal survival.

Standards for educational and psychological testing

Abstract: Pedagosko i psiholosko testiranje i procjenjivanje spadaju među najvažnije doprinose znanosti o ponasanju nasem drustvu i pružaju temeljna i znacajna poboljsanja u odnosu na ranije postupke. Iako se ne može ustvrditi da su svi testovi dovoljno usavrseni niti da su sva testiranja razborita i korisna, postoji velika kolicina informacija koje ukazuju na ucinkovitost kvalitetnih instrumenata u onim situacijama u kojima je njihovo koristenje potkrijepljeno validacijskim podacima. Pravilna upotreba testova može dovesti do boljih odluka o pojedincima i programima nego sto bi to bio slucaj bez njihovog koristenja, a također i ukazati na put za siri i pravedniji pristup obrazovanju i zaposljavanju. Međutim, losa upotreba testova može dovesti do zamjetne stete nanesene ispitanicima i drugim sudionicima u procesu donosenja odluka na temelju testovnih podataka. Cilj Standarda je promoviranje kvalitetne i eticne upotrebe testova te uspostavljanje osnovice za ocjenu kvalitete postupaka testiranja. Svrha objavljivanja Standarda je uspostavljanje kriterija za evaluaciju testova, provedbe testiranja i posljedica upotrebe testova. Iako bi evaluacija prikladnosti testa ili njegove primjene trebala ovisiti prvenstveno o strucnim misljenjima, Standardi pružaju okvir koji osigurava obuhvacanje svih relevantnih pitanja. Bilo bi poželjno da svi autori, sponzori, nakladnici i korisnici profesionalnih testova usvoje Standarde te da poticu druge da ih također prihvate.

W/kit gene required for interstitial cells of Cajal and for intestinal pacemaker activity

Abstract: The pacemaker activity in the mammalian gut is responsible for generating anally propagating phasic contractions. The cellular basis for this intrinsic activity is unknown. The smooth muscle cells of the external muscle layers and the innervated cellular network of interstitial cells of Cajal, which is closely associated with the external muscle layers of the mammalian gut, have both been proposed to stimulate pacemaker activity. The interstitial cells of Cajal were identified in the last century but their developmental origin and function have remained unclear. Here we show that the interstitial cells of Cajal express the Kit receptor tyrosine kinase. Furthermore, mice with mutations in the dominant white spotting (W) locus, which have cellular defects in haematopoiesis, melanogenesis and gametogenesis as a result of mutations in the Kit gene, also lack the network of interstitial cells of Cajal associated with Auerbach's nerve plexus and intestinal pacemaker activity.

Regulation of cell fate decision of undifferentiated spermatogonia by GDNF.

Abstract: The molecular control of self-renewal and differentiation of stem cells has remained enigmatic. Transgenic loss-of-function and overexpression models now show that the dosage of glial cell line-derived neurotrophic factor (GDNF), produced by Sertoli cells, regulates cell fate decisions of undifferentiated spermatogonial cells that include the stem cells for spermatogenesis. Gene-targeted mice with one GDNF-null allele show depletion of stem cell reserves, whereas mice overexpressing GDNF show accumulation of undifferentiated spermatogonia. They are unable to respond properly to differentiation signals and undergo apoptosis upon retinoic acid treatment. Nonmetastatic testicular tumors are regularly formed in older GDNF-overexpressing mice. Thus, GDNF contributes to paracrine regulation of spermatogonial self-renewal and differentiation.