The intercalated cells (ITCs) of the amygdala have been shown to be critical regulatory components of amygdalar circuits, which control appropriate fear responses. Despite this, the molecular processes guiding ITC development remain poorly understood. Here we establish the zinc finger transcription factor Tshz1 as a marker of ITCs during their migration from the dorsal lateral ganglionic eminence through maturity. Using germline and conditional knock-out (cKO) mouse models, we show that is required for the proper migration and differentiation of ITCs. In the absence of, migrating ITC precursors fail to settle in their stereotypical locations encapsulating the lateral amygdala and BLA. Furthermore, they display reductions in the ITC marker Foxp2 and ectopic persistence of the dorsal lateral ganglionic eminence marker Sp8. mutant ITCs show increased cell death at postnatal time points, leading to a dramatic reduction by 3 weeks of age. In line with this,-null mutants also show a loss of ITCs at postnatal time points, suggesting that may function downstream of in the maintenance of ITCs. Behavioral analysis of male cKOs revealed defects in fear extinction as well as an increase in floating during the forced swim test, indicative of a depression-like phenotype. Moreover, cKOs display significantly impaired social interaction (i.e., increased passivity) regardless of partner genetics. Together, these results suggest that plays a critical role in the development of ITCs and that fear, depression-like and social behavioral deficits arise in their absence. We show here that the zinc finger transcription factor Tshz1 is expressed during development of the intercalated cells (ITCs) within the mouse amygdala. These neurons have previously been shown to play a crucial role in fear extinction. mouse mutants exhibit severely reduced numbers of ITCs as a result of abnormal migration, differentiation, and survival of these neurons. Furthermore, the loss of ITCs in mouse mutants correlates well with defects in fear extinction as well as the appearance of depression-like and abnormal social interaction behaviors reminiscent of depressive disorders observed in human patients with distal 18q deletions, including the locus.

The protein tyrosine phosphatase Shp2 (PTPN11) is crucial for normal brain development and has been implicated in dorsal telencephalic neuronal and astroglia cell fate decisions. However, its roles in the ventral telencephalon and during oligodendrogenesis in the telencephalon remain largely unknown. Shp2 gain-of-function (GOF) mutations are observed in Noonan syndrome, a type of RASopathy associated with multiple phenotypes, including cardiovascular, craniofacial, and neurocognitive abnormalities. To gain insight into requirements for Shp2 (LOF) and the impact of abnormal Shp2 GOF mutations, we used a Shp2 conditional mutant allele (LOF) and a cre inducible Shp2-Q79R GOF transgenic mouse in combination with Olig2 cre/ϩ mice to target embryonic ventral telencephalic progenitors and the oligodendrocyte lineage. In the absence of Shp2 (LOF), neuronal cell types originating from progenitors in the ventral telencephalon were generated, but oligodendrocyte progenitor cell (OPC) generation was severely impaired. Late embryonic and postnatal Shp2 cKOs showed defects in the generation of OPCs throughout the telencephalon and subsequent reductions in white matter myelination. Conversely, transgenic expression of the Shp2 GOF Noonan syndrome mutation resulted in elevated OPC numbers in the embryo and postnatal brain. Interestingly, expression of this mutation negatively influenced myelination as mice displayed abnormal myelination and fewer myelinated axons in the white matter despite elevated OPC numbers. Increased proliferating OPCs and elevated MAPK activity were also observed during oligodendrogenesis after expression of Shp2 GOF mutation. These results support the notion that appropriate Shp2 activity levels control the number as well as the differentiation of oligodendrocytes during development.

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63 Background: Adolescent and young adults (AYA) diagnosed with cancer have distinct physical, developmental and psychosocial needs that are often unmet during oncology treatment. Such needs are further intensified for AYA patients with an advanced cancer diagnosis. Palliative Care (PC), specialized care for patients and families with serious illness, can address these needs throughout the disease trajectory including symptom management, supportive communication, and advance care planning. The incorporation of PC remains suboptimal despite evidence that palliative services can improve quality of life. In an effort to identify strategies to advance access to PC for the AYA population at our institution, the referral pattern to PC was studied. Methods: A retrospective chart review was performed to identify referral patterns to PC in the AYA population (ages 18-39) from July 2017 through June 2019 at a National Cancer Institute designated comprehensive cancer center. Descriptive statistics were utilized to summarize referral patterns and trends. Results: In the past 2 years, 1,894 AYA patients established oncology care at our institution. The most common AYA cancer diagnoses included hematologic 20.8% (n=944), thyroid 10.8% (n=490), brain 9.9% (n=451) and breast 9.1% (n=414). There were 311 (16%) referrals placed to PC, mostly in the inpatient setting (81.4%). Less than half (43%) of the inpatient referrals had a post-discharge follow-up appointment in the PC clinic. Multiple disease-specific service lines were represented including leukemia (40%), colorectal (14.5%), sarcoma (9%) and breast (9%). Quarterly volumetric trends remained static over the 2 years (average number of referrals: 54/quarter). The average age at cancer diagnosis in the AYA population was 30 years and 32.7 years (range 19-39) at time of PC referral. This was consistent with the average length of time from initial diagnosis to PC referral of 2.8 years. Conclusions: Comprehensive oncology care in the AYA population should include PC. Yet, involvement of PC in the AYA population during oncologic treatment was limited. Future research will investigate optimal models of integrative PC to address the unique needs of AYA cancer.

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