Three cell types differentiate in the early frog neural plate: neural crest at the lateral edges, floorplate at the midline and primary neurons in three bilateral stripes. Floorplate cells and ventral neurons are induced by Sonic hedgehog (Shh) and neural crest and dorsal neurons are induced by epidermal factors such as bone morphogenetic proteins (BMPs). Neurogenesis in a subset of cells within the stripes involves lateral inhibition. However, the process by which pools of precursors are defined in stereotypic domains in response to inductive signals is unknown. Here we show that frog Zic2 encodes a zinc-finger transcription factor of the Gli superfamily which is expressed in stripes that alternate with those in which primary neurons differentiate and overlap the domains of floorplate and neural crest progenitors. Zic2 inhibits neurogenesis and induces neural crest differentiation. Conversely, Gli proteins are widely expressed, induce neurogenesis and inhibit neural crest differentiation. Zic2 is therefore a vertebrate pre-pattern gene, encoding anti-neurogenic and crest-inducing functions that counteract the neurogenic but not the floorplate-inducing activity of Gli proteins. We propose that the combined function of Gli/Zic genes responds to inductive signals and induces patterned neural cell differentiation.

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Mammographic density has been established as an independent risk factor for breast cancer, and there is data to suggest that the degree of lobular involution in the breast tissue may also function as an independent risk factor for the disease. The present study was designed to investigate the relationship between mammographic density and lobular involution in a population of mature women undergoing open biopsy for non-palpable breast lesions.A total of 199 women over the age of 60 who underwent breast biopsy with image-guided localization in 2008 at NYU Langone Medical Center formed the study population. Variables of interest included age, breast density, degree of involution, use of hormone replacement therapy (HRT) and biopsy histology (invasive ductal and lobular carcinoma and intraductal carcinoma vs. benign). Breast density was categorized according to BI-RADS classification as less dense (predominantly fatty and scattered fibroglandular elements) vs more dense (heterogeneously dense and extrememely dense). Degree of involution was classified as none (0%), partial (1-74%) and complete (>75%). All specimens were reviewed by a single pathologist who used the criteria of Hartmann, et al in evaluating degree of involution. Statistical analysis was performed using Pearson's Chi-square test and logistic regression analyses.In agreement with our previously presented data, we found an inverse relationship between breast density and age (p=0.02). In our cohort of women over 60 with abnormal breast imaging, we found a trend toward an inverse relationship between age and degree of lobular involution, but this did not achieve statistical significance. 129 of our patients had biopsies yielding malignant histology. There was no significant relationship between degree of lobular involution and biopsy histology. Use of HRT did not correlate with breast density in our cohort. There was no discernable relationship between degree of involution and history of prior or current HRT use.Association of lobular involution with age, density, histology, and HRT  INVOLUTION TOTALP-VALUE NONEPARTIALCOMPLETEN (%) AGE (YRS)      60-696337617 (9%)0.18270-797202959 (29%) 80-894618123 (62%) DENSITY     Less Dense143477125 (63%)0.177More Dense3254674 (37%) HISTOLOGY     Benign5194670 (35%)0.690Malignant124077129 (65%) HRT     Never11246398 (70%)0.774Ever3112741 (30%)  Our study reinforces the general observation that breast density decreases with age. Our data do not permit us to comment on the validity of lobular involution as a risk factor for breast cancer. However, the degree of lobular involution did not predict malignant histology in our cohort. There was a trend toward an inverse relationship between mammographic density and lobular involution. This observation suggests that other factors such as stromal features may be responsible for the increased mammographic density in these older patients. Further study is warranted to better understand the significance of lobular involution and its relationship with mammographic density in all age groups of women undergoing breast cancer screening. Citation Information: Cancer Res 2009;69(24 Suppl):Abstract nr 6072.